Week 5: Tumor Immunology

Question 1

Define the term proto-oncogene

Answer 1

Normal genes that initiate or maintain cell division that may become cancer
genes

Question 2

Lymph nodes are part of the peripheral lymphoid tissue, name two other examples

Answer 2

Lymph nodes, spleen, mucosal and cutaneous immune system

Question 3

Where are T and B lymphocytes located in lymph nodes, and how is their anatomic separation maintained?

Answer 3

B lymphocytes reside in follicles in peripheral (secondary) lymphoid organs.
T cells reside in the parafollicular cortex of lymph nodes. B and T cells are
maintained in these locations by specific cytokines called chemokines, which
are secreted by stromal cells in the follicle and the parafollicular cortex,
respectively.

Question 4

What are the main two main classifications of tumour antigens that the immune system reacts against?

Answer 4

Tumours express many mutated proteins that may appear foreign to the immune system and induce immune responses. Tumours may overexpress or inappropriately express antigens that are normally expressed only at low
levels in normal tissues or only during development and therefore do not induce tolerance. Some tumours caused by oncogenic viruses may express viral antigens that induce immune responses. They can be considered:
Products of Mutated Oncogenes and Tumour Suppressor Genes
Products of Other Mutated Genes Overexpressed or Aberrantly Expressed Cellular Proteins
· Tumour Antigens Produced by Oncogenic Viruses
· Oncofetal Antigens
· Altered Cell Surface Glycolipids and Glycoproteins
· Cell Type-Specific Differentiation Antigens

Question 5

How do naive CD8+ T cells recognize tumour antigens, and how are these cells activated to differentiate into effector CTLs?

Answer 5

Naive CD8+ T cells recognize tumour antigens in the same way they recognize microbial antigens: by T cell receptor (TCR) binding to tumourderived peptides displayed on class I MHC molecules on dendritic cells. This means the DC must internalize tumour cells (or their products) and process the internalized tumour proteins by the class I MHC pathway, which involves proteasomal degradation of the proteins into peptides. The presentation of peptides derived from internalized proteins on class I MHC molecules is called cross-presentation. The DC displays not only tumour-derived peptide antigens to naive CD8+ T cells but also costimulators. The combination of antigen and costimulators activates clonal expansion and differentiation of the naive CD8+ T cells into effector cytotoxic T lymphocytes.

Question 6

What risk factors are associated with malignant melanoma?

Answer 6

UV exposure and sun burn, number of moles,
skin type, previous melanomas previous SCC or BCC,
first-degree relative diagnosed with melanoma
Compromised immune systems as the result of chemotherapy, an organ transplant, excessive sun exposure, and diseases such as HIV/AIDS or lymphoma can increase your risk of melanoma.

Question 7

What is the difference between grade of tumour and staging of a tumour?

Answer 7

Grading refers to the differentiation of the tumour with respect to the tissue from which it originates. Staging refers to the extent to which the tumour has spread and takes into account: the local extent of the tumour (T status), lymph node metastasis (N status) and distant organ metastasis (M status).

Question 8

What, in general terms, are immunotherapies for cancer?

Answer 8

Therapies that harness the innate functions of the immune system

Question 9

What are the 6 functional domains of antibody structure

Answer 9

1. F ab region
2. F c region
3. heavy chain with one variable (Vh) domain followed by a constant domain, a hinge region, and two more constant domains
4. light chain with one variable and one constant
5. antigen binding site
6. hinge region

Question 10

What tracer is typically used in oncology PET

scans to add contrast to the images? Why would cancer cells take up more of this tracer?

Answer 10

FDG (fluorodeoxyglucose)
This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly growing malignant tumours).

Question 11

Opioids given as pain control go through first pass metabolism.

What does this mean and how can this be avoided

Answer 11

First pass metabolism is where blood from the gut reaches the liver by the portal system, where the liver could metabolise the drug before it gets to the
systemic circulation. It can be avoided by parenteral route and sublingual or rectal route of administration.

Question 12

Explain how tachyphylaxis can occur in the chronic treatment of patients with opiates.

Answer 12

Repeated use of an opioid causes mu receptors to become down-regulated and tachyphylaxis to occur requiring more opioid required to elicit same response.

Question 13

You are working in a GP practice. Mr Grant a 70 year old man has recently been diagnosed with lung cancer. He has booked an appointment with you as he has some questions about his new diagnosis.

Mr Grant says he has read that the body’s immune system can fight off cancer. He asks why this hasn’t happened with him, and why he has a tumour on the lung. You explain that tumours are a bit like a parasite,
and they have mechanisms to prevent them from being eliminated from the host (you). What are some of these mechanisms?

Answer 13

· Weak antigenicity
· Immunosuppression and tolerance induction
· Release soluble antigens
· Antigen-antibody complexes
· Antigenic variation

Question 14

Name two types of genes that can be affected by mutations and result in unregulated cell growth

Answer 14

· Oncogene

· Tumour suppressor gene

Question 15

You are working in a GP practice. Mr Grant a 70 year old man has recently been diagnosed with lung cancer. He has booked an appointment with you as he has some questions about his new diagnosis. Mr Grant asks what factors can result in mutations that lead to tumours. You explain that mutations can result from inherited factors
or from exposure to chemicals in the environment- give some examples of each of these:

Answer 15

Inherited:
· Breast cancer BRCA1 and BRCA2 genes
· Bowel cancer
o Familial adenomatous polyposis (FAP)caused by a
fault in the APC gene
o Peutz Jeghers syndrome (PJS) linked to a gene fault called STK11
· Melanoma CDKN2A gene

Exposure to chemicals in the environment
· Asbestos mesothelioma
· Aniline dyes and bladder transitional cell cancer (TCC)
· Smoking lung cancer
· Sun- skin cancer

Question 16

As smoking is associated with lung cancer and sun exposure is associated with skin cancer, which cancers are associated with asbestos exposure?

Answer 16

mesotheliomas

Question 17

As smoking is associated with lung cancer and sun exposure is associated with skin cancer, exposure to which occupational chemical is associated with bladder transitional cell cancer?

Answer 17

Aniline dyes and bladder transitional cell cancer (TCC)

Question 18

How are natural killer cells unique compared to other cells in the immune system with regards to the types of cells they are able to recognise?

Answer 18

NK cells are able to recognise cells that do not express MHC molecules. This is useful as many tumours do not express MHC molecules, which helps them to evade the immune system response.

Question 19

When macrophages and natural killer cells are activated against tumours they can cause cytostasis and/or cytolysis. What do these terms mean?

Answer 19

· Cytostasis: inhibition of cell growth and multiplication, preventing growth of the tumour

· Cytolysis: dissolution or disruption of cells, effectively killing the tumour

Question 20

Two non-specific immunotherapies that have been used for cancer are BCG and coleys toxin. How are these thought to work?

Answer 20

By activating macrophages, NK cells, cytokines that then attack tumours.

Question 21

Imagine that you have been given the task to make a

drug to target and destroy tumour cells using immunotherapy. What could your drug target and what would it do?

Answer 21

Diagram: cytokines activate NKC and macrophages, which target tumour cells.

You could create a drug that results in activation of cytokines: these activate NK cells and macrophages which can target the tumour cell. You could create an antibody that would target the tumour cell – once you
have an antibody that targets tumour cells you could couple it with a cytotoxic drug- this would mean that cytotoxic drugs would be in high levels around the tumour, and lower concentrations in other areas of the body, this would reduce the side effects of cytotoxic drugs.

You could create a drug that would reduce the regulatory mechanisms that limit immune response- this would result in a more effective immune response to tumours

Question 22

Mr Grant says he had a friend who was diagnosed with bowel cancer after having a blood test. He asks how that is possible. How would you explain this?

Answer 22

You explain that tumours can produce antigens, that if present in high levels in the blood can indicate a certain type of tumour cell is present and producing these antigens. These antigens are also known as tumour markers.

Question 23

What cancers are linked with the following tumour markers?

CEA

CA125

CA 19-9

Answer 23

CEA - colon cancer

CA125 - ovarian cancer

CA 19-9 - pancreatic cancer

Question 24

What tumour markers are linked with the following cancers?

• colon cancer
• ovarian cancer
• pancreatic cancer

Answer 24

CEA - colon cancer

CA125 - ovarian cancer

CA 19-9 - pancreatic cancer

Question 25

Name five cancers that have been firmly linked to viruses, and name the viruses they are linked to:

Answer 25

· Burkitts lymphoma and nasophryngeal carcinoma- EBV · Karposi’s sarcoma KSHV · Hepatocarcinoma HBV · Cervical cancer - papillomavirus

Question 26

Cancer occurs when the DNA sequence within a gene is altered in such a way that the gene can no longer instruct the cell in which it resides to produce the normal version of the protein it encodes. What are the three major factors are known to initiate tumour development:

Answer 26

􀁸 Chemical carcinogens: Many natural as well as man-made compounds 􀁸 Ionising radiation 􀁸 Viruses

Question 27

Regardless of how tumour development is initiated, the consequence is:

Answer 27

􀁸 Uncontrolled growth, resulting either from the abnormally high expression of genes which stimulate cell proliferation (ONCOGENES) 􀁸 Defective expression of genes which normally control proliferation (Tumour Suppressor Genes) 􀁸 Defective respond to apoptosis mechanisms

Question 28

The theory of immune surveillance suggested that which division of the immune system destroy newly appearing neoplastic cells?

Answer 28

The theory of immune surveillance suggested that the adaptive immune system, particularly cell-mediate immunity (CMI), destroy newly appearing neoplastic cells as a result of the new antigens they tend to express.

Question 29

True or false? Many tumours can be shown to express cell surface antigens which are not expressed in the normal progenitor cells before the neoplastic transformation event.

Answer 29

True If the immune system is able to detect tumours then tumours must express antigens that the body detects as non-self-antigens.

Question 30

Many tumours can be shown to express cell surface antigens which are not expressed in the normal progenitor cells before the neoplastic transformation event. These antigens have been categorized based on their nature and distribution into which categories?

Answer 30

•Tumour specific Antigens > chemically induced > virally induced •Tumour associated antigens > oncofetal tumour antigens > oncogene proteins 􀁸 Tumour-Specific Transplantation Antigens, or TSTA. chemical or radiation induced tumours express a unique neo-antigen, different from other tumours induced by the same or different agent. 􀁸 Tumour-Associated Transplantation Antigens (TATA). Tumours induced by oncogenic virus express virally encoded membrane antigens 􀁸 Onco-fetal antigens: antigens are selectively expressed on tumours, but are also shared with some normal foetal or embryonic tissues. Thought to reflect their reversion to a less fully differentiated state. 􀁸 Some tumour antigens are oncogene proteins.

Question 31

What are Tumour-Specific Transplantation Antigens, or TSTA?

Answer 31

Tumor antigens that are products of diverse mutated genes. Generally chemical or radiation induced tumours express a unique neo-antigen, different from other tumours induced by the same or different agent. These have been termed Tumour-Specific Transplantation Antigens, or TSTA.

Question 32

What are Tumour-Associated Transplantation | Antigens (TATA)?

Answer 32

Tumours induced by oncogenic virus express virally encoded membrane antigens, termed Tumour-Associated Transplantation Antigens (TATA).

Question 33

What is the difference between Tumour-Specific Transplantation Antigens (TSTA) and Tumour-Associated Transplantation Antigens (TATA)?

Answer 33

Generally chemical or radiationinduced tumours express a unique neo-antigen, different from other tumours induced by the same or different agent. These have been termed Tumour-Specific Transplantation Antigens, or TSTA. Tumours induced by oncogenic virus express virally encoded membrane antigens, termed Tumour-Associated Transplantation Antigens (TATA).

Question 34

What are Onco-fetal antigens?

Answer 34

Onco-fetal antigens: These antigens are selectively expressed on tumours, but are also shared with some normal foetal or embryonic tissues. Expression of such antigens by tumours is thought to reflect their reversion to a less fully differentiated state.

Question 35

Once the body has recognised a tumour antigen it must try and destroy that cell. This is principally achieved by which cell types?

Answer 35

APCs ingest tumour cells and present the antigens on T cells. CTLs specifically against the tumour antigens. PROCESS: APCs ingest tumour cells and present the antigens on T cells. Given that tumours occur in nucleated cells they are normally presented on Class I MHCs. Once naïve CD8+ T cells have differentiated into effector CTLs complex signalling cascade results in them releasing granzymes and perorins FAS and FABL that all assist in the destruction of tumour cells.

Question 36

Once the body has recognised a tumour antigen it must try and destroy that cell. Describe this process.

Answer 36

APCs ingest tumour cells and present the antigens on T cells. Given that tumours occur in nucleated cells they are normally presented on Class I MHCs. Once naïve CD8+ T cells have differentiated into effector CTLs complex signalling cascade results in them releasing granzymes and perorins FAS and FABL that all assist in the destruction of tumour cells.

Question 37

List the name of 4 processes by which tumours evade the immune system

Answer 37

``` Tolerance Immunomodulation Immunoselection Enhancing Antibodies Immuno-stimulation Blocking Factors Immuno-suppression Concomitant Immunity ```

Question 38

Evasion of Immune Response by Tumours: What is Tolerance?

Answer 38

A state of immunological tolerance may be promoted by the presence of very high levels of tumours antigens, particularly soluble forms which may be shed into the serum by tumour cells.

Question 39

Evasion of Immune Response by Tumours: What is Immunomodulation?

Answer 39

Antibody binding to a membrane antigen on either normal or neoplastic cells may result in the disappearance of that antigen from the cell surface either by endocytosis or by shedding. Once a tumour cell has lost its neoantigen, it becomes invisible to the immune system.

Question 40

Evasion of Immune Response by Tumours: What is Immunoselection?

Answer 40

Variant cells can appear in a tumour population which have lost a particular antigen through a mutational event; such a variant will have a selective advantage in the face of an even slightly effective immune response, and cells with the antigen-negative phenotype will therefore tend to progressively take over the population.

Question 41

Evasion of Immune Response by Tumours: What is Antibodies Enhancement?

Answer 41

Most nucleated cells are relatively resistant to complement-mediated lysis, and destruction of grafted tissue is largely the role of cell-mediated immunity. However, if antibodies are present which can bind to neoantigens, they may effectively "hide" these antigens which might otherwise serve as targets for T-cell-mediated killing, and thus "enhance" the survival of such cells.

Question 42

Evasion of Immune Response by Tumours: What is Immuno-stimulation?

Answer 42

Antibodies binding to tumour cells may also, in some cases, actually stimulate cell growth, through the generation of receptor mediated proliferative signals.

Question 43

Evasion of Immune Response by Tumours: What are Blocking Factors?

Answer 43

Soluble factors in the serum of tumour patients which can inhibit an existing immune response from affecting the tumour. The best characterised “blocking factors” have turned out to consist of circulating antigen-antibody complexes containing tumour antigens, which may blind or divert the immune response in ways which are still poorly understood.

Question 44

Evasion of Immune Response by Tumours: What is Immuno-suppression?

Answer 44

Tumour- patients often exhibit a substantial degree of generalised immunosuppression, resulting directly or indirectly from inhibitory cytokines and other substances secreted by the tumour (e.g. Hodgkin's lymphoma).

Question 45

Evasion of Immune Response by Tumours: What is Concomitant Immunity?

Answer 45

‘Concomitant immunity’ is described as an immune rejection reaction occurring at one site, co-existing with the progressive growth of an antigenically identical tumour elsewhere in the organism.

Question 46

What are Lymphoproliferative Disorders?

Answer 46

The normal response of immune cells to infection or inflammation is to undergo reactive polyclonal proliferation. Monoclonal expansion can give rise to leukaemia, lymphomas or myeloma. A clone of malignant cells (lymphoid, myeloid or monocytic) originating in the bone marrow is called a leukaemia. Malignant cells (blasts) may be seen in the peripheral blood.

Question 47

A clone of malignant cells | originating in the bone marrow is called a ....

Answer 47

leukaemia Could be lymphoid, myeloid or monocytic

Question 48

Define Lymphomas

Answer 48

Lymphomas are tumours of lymphoid cells originating in the peripheral lymph tissues. These malignant cells may infiltrate the spleen, liver, brain, bone marrow and lungs. Leukaemia and lymphomas arise from a single cell which has undergone malignant transformation leading to uncontrolled division into a clone of identical cells.

Question 49

What is acute leukaemia?

Answer 49

Acute leukaemia is the clonal proliferation of haematopoietic cells that results in an excess of immature cells and leads to functional bone marrow failure. Acute leukaemia is broadly classified as acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL).

Question 50

Acute leukaemia is broadly classified as which two conditions?

Answer 50

acute myeloid leukaemia (AML) acute lymphoblastic leukaemia (ALL).

Question 51

What is Chronic Myeloid Leukaemia?

Answer 51

Chronic myeloid leukaemia (CML) is a clonal disorder in which cells of the myeloid lineage undergo inappropriate clonal expansion. The disease progresses through three distinct phases – chronic phase, accelerated phase, and blast crisis – during which the leukemic clone progressively loses its ability to differentiate.

Question 52

What are the three phases of Chronic Myeloid Leukaemia?

Answer 52

The disease progresses through three distinct phases – chronic phase, accelerated phase, and blast crisis – during which the leukemic clone progressively loses its ability to differentiate.

Question 53

In which phase of chronic myeloid leukaemia do patients most commonly present ?

Answer 53

CML presents in the chronic phase in about 90% of patients. Many are asymptomatic and discovered incidentally. Common non-specific symptoms include fatigue, night sweats, weight loss, or spontaneous bruising or bleeding, splenomegaly, splenic infarction, anaemia, or platelet dysfunction.

Question 54

Symptoms of Chronic Myeloid Leukaemia?

Answer 54

Many are asymptomatic and discovered incidentally. Common non-specific symptoms include fatigue, night sweats, weight loss, or spontaneous bruising or bleeding, splenomegaly, splenic infarction, anaemia, or platelet dysfunction.

Question 55

What is Chronic lymphocytic leukaemia (CLL)?

Answer 55

lymphocytic Leukaemia - A clone of malignant cells (in this case lymphoid) originating in the bone marrow Chronic lymphocytic leukaemia (CLL) is the commonest leukaemia in the Western world. It is a disease of the elderly and is usually incurable except in a minority of patients suitable for allogeneic haematopoietic stem cell transplantation.

Question 56

The lymphomas form a group of neoplasms in which the malignant cells derive from lymphocytes. When early progenitor B- or T-cells are involved, the patient presents with which type of lymphoma or leukaemia?

Answer 56

acute lymphoblastic leukaemia (ALL) or | lymphoblastic lymphoma.

Question 57

The lymphomas form a group of neoplasms in which the malignant cells derive from lymphocytes. The final stage in B-cell maturation following antigen encounter leads to the production of memory cells and plasma cells, the cancerous equivalent of which is...

Answer 57

myeloma.

Question 58

How are lymphomas categorised as Hodgkins or non-Hodgkins?

Answer 58

Approximately 15% of lymphomas are termed Hodgkin's lymphomas (HL), identified on histopathological grounds. All other lymphomas are termed Non-Hodgkin's lymphomas (NHL). They represent a highly heterogeneous group with around 40 entities (World Health Organization classification), although a few common types predominate

Question 59

Is risk of developing Hodgkins or non-Hodgkins lymphoma increased in congenital and acquired immunodeficiency states?

Answer 59

Workbook seems to be conflicting on this. pg. 86. The risk of developing NHL is increased in congenital and acquired immunodeficiency states, including human immunodeficiency virus (HIV) infection, other immune disorders, such as rheumatoid arthritis, and post-transplantation. Hodgkin's - It is more frequently seen in other immunodeficient states, including post-organ transplant, immunosuppressive therapy and primary immunodeficiency states including autoimmune lymphoproliferative syndrome and ataxia telangiectasia.

Question 60

Why might Various infectious agents be associated with lymphoma?

Answer 60

chronic antigenic stimulation forming one step in a multi-step carcinogenic process

Question 61

What time of lymphoma is associated with epstein-Barr virus?

Answer 61

Epstein–Barr virus (EBV) is associated with Burkitt's lymphoma, prevalent in malarial areas of sub-Saharan Africa but rare in developed countries, and is present in two-thirds of HIV related lymphomas.

Question 62

List 3 viruses strongly associated with lymphomas

Answer 62

Epstein–Barr virus (EBV) is associated with Burkitt's lymphoma, Hepatitis C virus (HCV) infection increases the risk of non-Hodgkins lymphoma 2.5-fold. 􀁸 Infection with human T-cell lymphoma virus 1 (HTLV1) causes a rare type of NHL (ATLL), but only in a small minority of chronic carriers. 􀁸 There is a strong association between Helicobacter pylori and lymphomas of Mucosa-Associated Lymphoid Tissue (MALT) in the stomach.

Question 63

Presentation of lymphomas

Answer 63

The most common presenting symptom is painless lymph node enlargement. Indolent lymphomas present with widespread, slowly progressive lymphadenopathy with few constitutional symptoms. Aggressive lymphomas present with rapidly enlarging lymph nodes and have associated constitutional (‘B’) symptoms (pyrexia, weight loss, night sweats).

Question 64

Why are patients routinely tested for HIV and hepatitis before commencing treatment for lymphoma?

Answer 64

Patients are routinely tested for HIV, hepatitis B virus (HBV) and HCV before the commencement of immunosuppressive NHL treatment, which can exacerbate these conditions

Question 65

Three types of Burkitt's Lymphoma

Answer 65

- Endemic BL - Sporadic BL - HIV-associated BL

Question 66

What are group is most associated with Burkitt's lymphoma?

Answer 66

Burkitt's lymphoma (BL) is a highly aggressive disease of children and young adults. In Endemic BL, the original disease described by Denis Burkitt, the peak incidence is between ages 4–7

Question 67

How do children with endemic Burkitt's Lymphoma present?

Answer 67

endemic regions in equatorial Africa and climatic factors. This region corresponds to that with endemic malaria. The peak incidence is between ages 4–7, and children typically present with rapidly enlarging tumours of the jaw or other facial bones. Extra-nodal involvement is frequent, especially ovaries, kidneys and breasts Most tumours are EBV-associated.

Question 68

How do children with Sporadic Burkitt's Lymphoma present?

Answer 68

The most common presentation is with an abdominal mass, especially of the ileo-caecal region. As in endemic BL, other extra-nodal involvement is frequent, especially ovaries, kidneys and breasts

Question 69

In what condition do most cases arise from the clonal proliferation of B lymphocytes and the majority of cases are curable?

Answer 69

Hodgkin Lymphoma

Question 70

Presentation of Hodgkin Lymphoma

Answer 70

Presentation includes a painless lymph node mass, often affecting the cervical chain although any nodal sites may be affected. Extra-nodal disease is less common and splenic or bone marrow involvement occurs only in the minority of cases. B symptoms (recurrent fevers, night sweats and loss of weight) affect a substantial proportion of cases.

Question 71

Two subtypes of Hodgkin Lymphoma

Answer 71

The disease has two subtypes: 􀁸 classical Hodgkin lymphoma 􀁸 nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) These are distinguished by their morphology and immune-phenotype and have certain clinical characteristics.

Question 72

In classical Hodgkin lymphoma, the malignant cell is termed a

Answer 72

Reed–Sternberg (RS) cell

Question 73

Reed–Sternberg (RS) cell

Answer 73

In classical Hodgkin lymphoma, the malignant cell is termed a Reed–Sternberg (RS) cell and is typically large with two (or more) nuclear lobes containing separate nucleoli often creating an ‘owl's eyes’ appearance. Mononuclear forms are termed Hodgkin cells.

Question 74

In classical Hodgkin lymphoma, the malignant cell is termed a Reed–Sternberg (RS) cell and is typically large with two (or more) nuclear lobes containing separate nucleoli often creating an ‘owl's eyes’ appearance. Mononuclear forms are termed....

Answer 74

Hodgkin cells.

Question 75

Describe the appearance of Reed– | Sternberg (RS) cells

Answer 75

typically large with two (or more) nuclear lobes containing separate nucleoli often creating an ‘owl's eyes’ the malignant cell in classical Hodgkin lymphoma

Question 76

Describe the particular requirements of transfusion after Hodgkin lymphoma

Answer 76

Hodgkin lymphoma confers long-term immune dysregulation associated with a risk of transfusion-associated graft-versus-host disease. This leads to a lifelong requirement for the irradiation of cellular blood products, to inactivate the residual lymphocytes that can cause this complication if transfusion is required.

Question 77

Myeloma

Answer 77

Myeloma is a clonal proliferation of bone marrow plasma cells that causes bone lesions, anaemia, renal failure and recurrent infections,

Question 78

What is the name of the condition in which a clonal proliferation of bone marrow plasma cells that causes bone lesions, anaemia, renal failure and recurrent infections?

Answer 78

Myeloma

Question 79

Presenting features of Myeloma

Answer 79

Presenting features are variable and non-specific and include anaemia (normocytic normochromic), bone pain, (osteolytic deposits or fractures), fatigue, weight loss, renal impairment (tubular blockage by cast nephropathy, amyloid deposition, dehydration, sepsis or use of nephrotoxic drugs), hypercalcaemia, hyper-viscosity (Can lead to blurred vision, headache, confusion and bleeding from mucous membranes) and recurrent infection (from immune-paresis due to the reduction of uninvolved immunoglobulins).

Question 80

Suggest mechanism through which monoclonal antibodies may be used to target cancer cells

Answer 80

Many are used as unconjugated ‘naked’ antibodies. Once antibodies have bound to a tumour antigen it will activate an effector mechanism such as the complement system, opsonisation, or by serving as antagonists for cell surface receptors important for cell proliferation or angiogenesis (growth of blood vessels). potential use of anti-tumour antibodies conjugated with toxins (e.g. diphtheria toxin, or the plant toxin ricin), or highly radioactive isotopes, thus serving as targeting agents to deliver these toxic molecules to tumour cells.

Question 81

Summarise Adoptive Cellular Therapies for Cancer

Answer 81

``` T lymphocytes are isolated from blood and grown in culture before being introduced back into the patient to act as part of the immune system. Lymphocytes removed from a tumour-bearing patient can be treated in vitro with lymphokines (e.g. IL-2), and the resulting ‘activated’ cells re-injected into the patient, in the hope that the tumour cells will be killed by tumourspecific killer T-cells present in the transfused cell population. ```

Question 82

Chimeric Antigen Receptor Treatment for Cancer

Answer 82

Chimeric antigen receptors are genetically introduced into a patient’s T cells in a lab and then reintroduced into the patient as a form of therapy. Stimulation of Host Anti-Tumour Immune Response. Some strategies have focused on promoting the immune responses against tumours or blocking inhibitory mechanisms that suppress anti-tumour immunity.

Question 83

Immunological Treatment for Cancer: Vaccination

Answer 83

Vaccination have been created using patients own tumour antigens, or antigens produced by stimulating dendritic cells (Remember that some tumours caused by oncogenic viruses can be prevented by vaccination e.g. Hep B and HPV see infection unit).

Question 84

Immunological Treatment for Cancer: Checkpoint Blockade

Answer 84

Blocking the inhibitory signals that control lymphocytes allows a more active host immune response Inhibit tumor-induced suppression of T-cell activation or function Antibodies target immune checkpoints to enhance antitumor response e.g. CTLA-4 and PD1 (programmed death 1)

Question 85

Immunological Treatment for Cancer: Cytokine Therapies

Answer 85

Cytokine have the ability to promote lymphocyte activity, however there can also be some severe toxic side effects. •Proteins that are naturally secreted by immune system cells •Mechanism of action –Interleukin-2 (IL-2) stimulates T-cell proliferation

Question 86

Define NEOPLASM

Answer 86

Abnormal growth of cells which persists after initiating stimulus has been removed •Cell growth has escaped from normal regulatory mechanisms

Question 87

4 stages of cell cycle

Answer 87

G1 - Growth S - DNA Synthesis G2 - growth and preparation for mitosis M - mitosis (cell division)

Question 88

What evidence do we have of the Role of the immune system in Cancer?

Answer 88

Examples: - Malignant tumors develop up to 20 fold more in individuals with compromised immune systems - T-cell infiltration within tumors predicts overall survival (OS) in multiple cancer types including bladder cancer

Question 89

Two types of tumour specific antigens

Answer 89

Chemically induced - Tumour-Specific Transplantation Antigens, or TSTA. virally induced - Tumour-Associated Transplantation Antigens (TATA).

Question 90

Two examples of Tumour associated antigens

Answer 90

* oncofetal tumour antigens (inappropriate expression of embryonic gene) * oncogene proteins

Question 91

All tumour antigens will be presented on what structure?

Answer 91

MHC I

Question 92

Tumour antigens will be presented on MHC I, which when bound to TCR, the CTL released what products?

Answer 92

Granzymes Perforins FAS-L

Question 93

What is an Oncovirus?

Answer 93

When a virus infects a cell, it expresses proteins that cause the cell to proliferate and/or block apoptosis

Question 94

The role of CD16 in antibody-dependent cell-mediated cytotoxicity (ADCC)

Answer 94

* Many cells involved in the innate immune responsealso express CD16 (Fc receptor), which is a low affinity receptor forimmunoglobulins such as IgG. * Immunoglobulin binding by CD16 targets innate immune cells to the immunonglobulin-bound target cell, and triggers target cell destruction.

Question 95

Immune system and cancer interact in a dynamic process, known as the 3 E’s. What are the 3 E's?

Answer 95

Elimination (immune system eradicates cancer cells) Equilibrium (immune system controls cancer outgrowth) Escape (cancer overwhelms the immune system)

Question 96

Tumour related mechanisms of escape (from immune surveillance)

Answer 96

Failure of tumour to provide a suitable antigenic target or an effective immune response. - lack of recognisable tumour antigen - lack of MHC 1 - deficit antigen processing - antigen modulation - antigenic masking of tumour - resistance of tumour to tumoricidal pathways - lack of co-stimulatory signals - production of inhibitory cytokines - shedding of tumour antigens

Question 97

House related mechanisms of escape (from immune surveillance)

Answer 97

Failure of host to recognise antigenic tumour cells. - immuno-suppresion or immunodeficiency - deficiency in inducing apoptosis and cell death signalling - infections or old age - deficiency in tumour antigen presentation by host APC - failure of host effector cells to reach the tumour (e.g. stroll barrier) - failure of host to kill variant tumour cells - T reg hindrance to tumour immunity

Question 98

Cancerous illness of white blood cells is called...

Answer 98

Leukaemia In leukaemia, white cells, instead of growing and developing normally, the white blood cells grow out of control but do not mature, which means they do not work properly.

Question 99

* acute myeloid leukaemia (AML), * acute lymphoblastic leukaemia (ALL), Are both derived from which progenitor cell?

Answer 99

both hematopoietic stem cells * acute myeloid leukaemia (AML) -> myeloid progenitor cell * acute lymphoblastic leukaemia (ALL) -> lymphoid progenitor cell

Question 100

What disease is Characterized by the abnormal proliferation B or T cells in lymphoid tissue causing lymphadenopathy?

Answer 100

Lymphoma

Question 101

Which type of lymphoma mainly affects adults; the risk increases with age?

Answer 101

Non-Hodgkin lymphoma

Question 102

Which type of lymphoma often affects young adults, most of whom can be cured, especially if diagnosed at an early stage?

Answer 102

Hodgkin lymphoma

Question 103

Coley toxins.

Answer 103

In late 1800s Dr William Coley first noted that getting an infection after surgery seemed to help some cancer patients. he began treating cancer patients by infecting them with certain kinds of bacteria, which came to be known asColey toxins.

Question 104

Cancer immunotherapy: Features of an Effective Immune Response

Answer 104

* Specificity - Ability to recognize and mount a specific response to distinct antigens * Trafficking - Ability of activated immune system cells to migrate to particular antigens throughout the body * Adaptability - Allows for a broader immune response (eg, immune response to additional antigens) * Target elimination - Ability of immune cells to destroy their target (eg, cancer cells) * Durability (immune memory) - Ability of immune system to recognize an antigen to which it has previously been exposed and provide long-lasting protection against it

Question 105

Features of an Effective Immune Response: examples of specificity

Answer 105

* Seasonal flu mutates surface antigens | * Annual vaccination allows the immune system to effectively recognize and target the specific flu strain

Question 106

Features of an Effective Immune Response: examples of trafficking

Answer 106

* Following exposure to activated APCs, naive T cells become activated * Activated T cells are mobilized to areas containing antigen

Question 107

4 main types of immunotherapy now being used to treat cancer

Answer 107

* Monoclonal antibodies (naked or conjugated) * Immune Checkpoint inhibitors * Therapeutic vaccines * Other non specific immunotherapies (cytokines, interleukins etc)

Question 108

Active vs passive cancer immunotherapy

Answer 108

Active: - engaged immune system, - durable - e.g. therapeutic cancer vaccines Passive - enhanced pre-existing immune response - short lived - examples: mABs, cytokines

Question 109

Very basic definition of Monoclonal Antibodies (mABs)

Answer 109

Proteins designed to bind to specific substances in the body

Question 110

What type of drug is Herceptin?

Answer 110

naked monoclonal antibody used in treatment of HER2 positive breast cancer.

Question 111

What is the function of HER2 receptors in breast cancer cells?

Answer 111

HER2 receptors send signals telling cells to grow and divide HER2+ breast cancer cells - too many HER2 receptors send more signals, causing cells to grow too quickly Herceptin (monoclonal antibody) may step the HER2 receptors from signalling the cell to grow