M10 Flashcards
neoplasms or the so-called cancers or malignancies
TUMOR
study of the relationship between the immune system and cancer cells.
TUMOR IMMUNOLOGY
Areas of concern of Tumor Immunology
The antigens associated with tumor cells
The host’s immune responses to tumors
Mechanisms by which tumors are thought to escape these responses
Therapeutic use of the immune system in an attempt to eradicate tumors.
Small, uniformly shaped nuclei
NORMAL CELL
Large, variable shaped nuclei
TUMOR
Relatively large cytoplasm volume
NORMAL CELL
Relatively small cytoplasmic volume
TUMOR
Uniform cell size and shape
NORMAL
Variation of cell size and shape
TUMOR
Organized arrangement of cells into tissues
NORMAL
Disorganized arrangement of cells
TUMOR
Normal presentation
NORMAL
Elevated expression of cell markers
TUMOR CELL
Lower levels of dividing cell
NORMAL
Large number of dividing cells
TUMOR
Clear demarcation
NORMAL
Poorly defined cell boundaries
TUMOR
Demarcation - outline
These cells have a smooth, non-fuzzy outline
TYPES OF TUMORS
Benign
Malignant
Malignant types
Carcinoma
Sarcoma
NENIGN
Small
Slow-growing
Non-invasive
Well-differentiated
Localized
Large
Fast-growing
Invasive
Poorly-differentiated
Can metastasize
MALIGNANT
forms in the skin or tissue cells that line the body’s internal organs, such as the kidneys and liver.
CARCINOMA
body’s connective tissue cells, which include fat, blood vessels, nerves, bones, muscles, deep skin tissue and cartilage.
sarcoma
____ is an antigenic substance produced in tumor cells that triggers an immune response in the host.
Tumor antigens
They can be broadly classified into two groups:
tumor-specific antigens (TSAs) and tumor- associated antigens (TAAs).
Unique to the tumor of an individual patient or shared by a limited number of patients with the same type of tumor
TUMOR-SPECIFIC ANTIGENS (TSAS)
Coded for by ____ that have undergone genetic mutations
viral oncogenes, host proto-oncogenes or tumor suppressor genes
well known example of TSA
BCR-ABL fusion protein
marker for a type of leukemia called Chronic Myeloid Leukemia.
Oncogene
BCR-ABL gene, there is a so-called
translocation
mutation that is formed by the combination of two genes, known as BCR and ABL (fusion gene).
BCR-ABL
The ABL gene is normally found on the long arm of
chromosome number 9,
BCR gene is also found on the long arm of
chromosome number 22.
The BCR-ABL gene contains instructions that tell the abnormal cell to produce too much of a protein called
tyrosine kinase
In a___, the ABL gene will move or will be cut and removed, and will attach to the BCR genes, forming a change chromosome 22.
translocation
This causes the chromosome 22 to become the so-called ____
Philadelphia chromosome.
The Philadelphia chromosome is also called the _____, which is a marker for Chronic Myelogenous Leukemia (CML).
BCR-ABL fusion gene
CML is an example of a____
tumor-specific antigen (TSA).
An ____ is a virus that can cause cancer.
oncovirus or oncogenic virus
Epstein-Barr virus (EBV)
Burkitt lymphoma
Hodgkin lymphoma
Leiomyosarcomas
Post-transplant lymphoproliferative disease
Nasopharyngeal carcinoma
Hepatitis B virus (HBV)
Hepatocellular carcinoma
Hepatitis C virus (HCV)
Hepatocellular carcinoma
Human herpes virus 8 (HHV-8)
Kaposi sarcoma
Human papilloma virus (HPV)
Cervical cancer
Other genital and anal cancers
Human T-lymphotropic virus I (HTLV-1)
Adult T-cell leukemia or lymphoma
Merkel cell polyomavirus
Merkel cell carcinoma (a type of skin cance
___are expressed in normal cells as well as in tumor cells
TAAs
Tumor cells abnormally express these protein or carbohydrate antigens in terms of their ____
concentration, location, or stage of differentiation.
TAAs can be a ___
peptide, glycolipid or glycoprotein antigen
peptide, glycolipid or glycoprotein antigen
three major peptide TAAs
Expressed in many tumors, but not in most normal tissues.
SHARED TSAs
The only normal cells in which they have been detected are testicular germ cells
SHARED TSAs
lesser extent, placental trophoblasts and ovaries.
SHARED TSAs
Expressed on immature cells of a particular lineage.
DIFFERENTIATION ANTIGENS
example of a TAA in this group is the
CD10 antigen
CD10 antigen (previously known as theor____)
common acute lymphoblastic leukemia antigen
normally found on pre-B cells but not on mature B cells.
common acute lymphoblastic leukemia antigen
expressed by melanoma tumors.
melanoma antigen gene (MAGE) proteins
____ that are normally expressed on developing cells of the fetus
oncofetal or embryonic antigens
There is a possibility of the presence of differentiation antigens if oncofetal or embryonic antigens are found in___
adult cells
Found in higher levels on malignant cells than on normal cells
OVEREXPRESSED ANTIGENS
Genetic mutations that occur during transformation are thought to deregulate expression of these proteins, resulting in levels up to ____ times greater than normal
100
well-known example of a TAA in this category is the ____, a transmembrane receptor that binds ____.
human epithelial growth factor receptor 2 (HER2) protein, human epidermal growth factor
Biological substances that are found in increased amounts in the ____ of patients with a specific type of cancer.
blood, body fluids, or tissues
proteins, carbohydrates, oncofetal antigens, hormones, metabolites, receptors, or enzymes
Tumor markers
___, which is common among men
prostate-specific antigen (PSA)
ideal tumor marker should have six characteristics. A marker should
Be produced by the tumor itself or by the patient’s body in response to the tumor
Be secreted into a biological fluid, where it can be inexpensively and easily quantified (e.g. blood and other bodily fluids)
Have a circulating half-life long enough to permit its concentration to rise with increasing tumor load.
Increase to clinically significant levels above the reference level while the disease is still treatable
Have a high sensitivity
Have a high specificity
Nonseminomatous testicular germ cell
Liver
Alpha-fetoprotein
(AFP)
Screening conducted in high-risk populations for liver cancer such as those with liver cirrhosis and chronic hepatitis
Alpha-fetoprotein
(AFP)
In ___, both AFP and hCG are elevated.
germ cell tumors
β2– microglobulin
B-lymphocyte malignancies
Part of class I MHC
molecule
β2– microglobulin
Higher levels imply poor prognosis in multiple myeloma.
β2– microglobulin
Familial medullary thyroid carcinoma
Calcitonin and
Serum Calcium
(Ca++)
MEDULLARY CARCINOMA
INCREASE:
DECREASE:
MEDULLARY CARCINOMA
INCREASE: CALCITONIN
DECREASE: SERUM CA++
WBC
CD markers
Colorectal
Breast
Lung
Carcinoembryonic
antigen (CEA)
Tissues of endodermal
origin
Carcinoembryonic
antigen (CEA)
Carcinoembryonic
antigen (CEA)
CONDITIONS
Renal failure
Nonneoplastic
liver and Intestinal disease
Age
Values increased with age and in smokers.
Carcinoembryonic
antigen (CEA)
Ovarian adenocarcinoma
Carbohydrate
Antigen (CA) 125
Carbohydrate
Antigen (CA) 125
CONDITIONS
Endometriosis
Pelvic inflammatory disease
Uterine fibroids
Pregnancy
Increases can occur during menstruation.
Screening is only recommended for women with a family history of ovarian cancer
Carbohydrate
Antigen (CA) 125
Breast cancer
Pancreatic, lung, colorectal, ovarian, and liver cancers
CA 15-3
Pancreatic
CA 19-9
Mammary tissue
CA 15-3
Benign breast disease
Benign liver disease
CA 15-3
CA 15-3 is a ____directed against an epitope of ___
monoclonal antibody ,episialin.
Benign hepatobiliary and pancreatic conditions
CA 19-9
Sialylated Lewisa blood group antigen
CA 19-9
Subjects who are
___persons cannot synthesize CA 19-9.
Lewisa-and Lewisb-
Breast adenocarcinoma
Estrogen or
Progesterone
receptors (ER/PR)
nonseminomatous
testicular cancer germ cell trophoblastic (hydatidiform
mole, choriocarcinoma)
Human Chorionic
Gonadotropin
(hCG)
Malignancies can produce free α and β chains as well as intact α and β dimer.
Human Chorionic
Gonadotropin
(hCG)
Growth factor gene
in all cells
HER2 (neu) or neu
_____are more strongly associated with prostate cancer
Decreased percent of free PSA and PSA velocity greater than 0.75 ng/mL/year
____ may be high when PTH is
elevated in parathyroid carcinoma.
Serum Ca++
PTH has a _____, so levels are done intraoperatively to ensure complete
parathyroid tumor removal.
short half-life
Patients with cirrhosis or hepatitis tend to have a____AFP.
higher or increased
High cell turnover conditions = increased cell death → increased cell creation
β2–microglobulin
The opposite happens in parathyroid carcinoma, ___
where both calcium and PTH are increased
The key cells involved in innate immune responses to tumors
NATURAL KILLER (NK) CELLS
Tumor cells become susceptible to killing by NK cells when they____ of class I MHC or they___expression of ligands that bind activating NK cell receptors.
downregulate (decrease) expression, upregulate (increase)
NK cells express CD16 receptors that bind the immobilized antibody and activate the release of _____
perforins and granzymes.
NK cells are also known as the ____
Large Granular Lymphocyte
NK cells could kill tumor cells via ____
Antibody-dependent Cellular Cytotoxicity (ADCC).
__ activated in vitro by IFN-γ have been shown to possess tumoricidal capabilities.
Macrophages
Mediates the primary mechanism of adaptive immunity against tumors.
CYTOTOXIC T CELL
CD8+ T cell responses specific for tumor antigens may require cross presentation of the tumor antigens by____
dendritic cells.
Activated by Dendritic cells by presenting tumor antigens in conjunction with class II MHC molecules
HELPER T CELL
May play a role in tumor immunity by secreting cytokines such as IL-2 and IFN-γ
HELPER T CELL
Tumors evade _____ by engaging inhibitory molecules that normally function to prevent autoimmunity or regulate immune responses to microbes.
antitumor T cell responses
____are immature myeloid precursors that accumulate in bone marrow, lymphoid tissues, blood, and tumors of tumor-bearing animals and cancer patients, and suppress innate and T cell-mediated antitumor immune responses
Myeloid-derived suppressor cells (MDSCs)
This phenomenon has been called____, implying that the immune response directs changes in tumors that help them evade the response
immunoediting
Immunoediting is thought to consist of three phases:____
elimination, equilibrium, and escape
essentially the same as the immunosurveillance concept of the immune system
ELIMINATION
In this phase, tumor cells are thought to enter a state of ____with the immune system, which keeps altered cells under control so that they are not clinically evident.
dynamic equilibrium
The dynamic interactions between the tumor and the immune system are thought to shape the ____, hence the term immunoediting.
phenotype of the tumor and its ultimate outcome
During the ___, mutations can occur in the genetically insatiable transformed cells
equilibrium phase
Some tumors downregulate the expression of tumor antigens or MHC molecules on the cell surface, making them less likely to be recognized by T cells.
ESCAPE
Some tumor antigens may also be masked by glycoproteins and glycolipids on the cell surface, making them inaccessible to the immune system.
ESCAPE
Some tumor cells have impaired cell surface binding to perforin or have defective apoptosis-inducing receptors such as Fas
ESCAPE
Tumor cells pretend as cells that are not capable of causing diseases.
Equilibrium
Tumor cells no longer pretend, rather, it will have a stronger control over the immune system
Escape
“Harness the ability of the immune system to destroy tumor cells”
IMMUNOTHERAPY
Immunotherapeutic methods can be classified into three major types:
Active immunotherapy
Passive immunotherapy
Adoptive immunotherapy
began the first systematic immunotherapy by stimulating the patient’s own immune system to respond to TAA
William Coley
Coley developed “Coley’s Toxin” which is a mixture of ____
killed S. pyogenes and killed Serratia marcescens
used to treat patients with inoperable bone and soft-tissue sarcomas
Coley’s Toxin
Involves the administration of soluble components of the immune system to boost the immune response
PASSIVE IMMUNOTHERAPY
Artificial immune components are introduced to the body, such as:
___
Cytokines
Monoclonal antibodies
Granulocyte colony
stimulating factor (G-CSF)
IFN-α
Granulocyte-macrophage colony stimulating factor (GM-CSF)
IL-2
Monoclonal antibodies in cancer immunotherapy have been directed against seven major categories of antigens:
CD antigens
Glycoproteins
Glycolipids
Carbohydrates
Vascular targets
Stromal and Extracellular antigens
Growth factors
Surface antigens on tumor cells
Opsonization
Complement-mediated cytotoxicity
ADCC
a MAb+ directed against the CD20 antigen on B cells: used to treat B -cell neoplasms
Rituximab,
a MAb directed against mature lymphocyte antigen, CD52; used to treat chronic lymphocytic leukemia and T-cell lymphomas
Alemtuzumab
Block signaling pathways involved in cell proliferation and survival
Cell surface receptors
a MAb directed against epidermal growth factor receptor (EGFR), used to treat colorectal cancer
Panitumumab
MAb directed against HER2, used to treat breast and gastroesophageal tumors with overexpressed HER2
Trastuzumab
Inhibit formation of blood vessels necessary for delivery of oxygen and nutrients to the tumor
Antigens involved in
angiogenesis
a MAb directed against vascular endothelial growth factor (VEGF); for treatment of glioblastoma, colon, lung, and renal cancers
Bevacizumab
Enhance anti-tumor-specific T-cell responses by preventing T-cell inhibition
Molecules that block T-cell activation and proliferation by binding to molecules on antigen-presenting cells
a MAb directed against CTLA-4 (cytotoxic T-lymphocyte antigen 4); for treatment of metastatic melanoma
Ipilimumab
MAbs directed against PD-1 (programmed death1); used to treat melanoma, colon cancer. and other tumors
Nivolumab and Lambrolizumab,
Deliver potent toxic molecules directly to tumor cells
Antibody–drug conjugates (immunotoxins) directed against TSAs
an immunotoxin directed against the CD30 antigen; used to treat Hodgkin lymphoma and systemic anaplastic large cell lymphoma
Brentuximab vedotin
an immunotoxin directed against the HER2 antigen; for treatment of HER2-positive metastatic breast cancer
Trastuzumab-DM1
This type of immunotherapy involves the transfer of immune cells that were previously exposed to a tumor, to cancer patients.
The transfer of these immune cells is thought to effectively assist the patient’s body in eliminating tumor cells.
ADOPTIVE IMMUNOTHERAPY
This type of immunotherapy involves the transfer of immune cells that were previously exposed to a tumor, to cancer patients.
The transfer of these immune cells is thought to effectively assist the patient’s body in eliminating tumor cells.
ADOPTIVE IMMUNOTHERAPY
This type of immunotherapy involves the transfer of immune cells that were previously exposed to a tumor, to cancer patients.
The transfer of these immune cells is thought to effectively assist the patient’s body in eliminating tumor cells.
ADOPTIVE IMMUNOTHERAPY
