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Immunology II > Tumor immunology > Flashcards

Tumor immunology Flashcards

1
Q

Define Tumors

A
  • relatively slow growth rate
  • somewhat differentiated cells
  • usually encapsulated, therefore they don’t spread
  • not fatal unless at critical sites such as brain or heart
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2
Q

Define Malignant tumors

A
  • undifferentiated cells
  • readily metastasize
  • usually fatal if untreated
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3
Q

Define Tumor specific antigens

A

TSA’s = antigens unique to a particular tumor and not present on normal cell types. arise as a result of point mutations or gene rearrangements

  • -> immune response targets - may be altered self proteins
  • -> not commonly seen in human tumors
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4
Q

Define Tumor-associated antigens

A

TAA’s = antigens shared by different tumors; also found on normal tissues

  • -> E.g - Oncofetal antigens: expressed on fetal, but not adult tissues
  • -> alpha fetal protein (AFP) = produced by certain liver cancers
  • -> carcinoembryonic antigen (CEA) = increased in colon cancer and smokers
    • Not therapeutic targets; useful for detection and monitoring treatment
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5
Q

Define Oncogenic viral antigens

A

Some RNA/DNA viruses –> tumors + viral antigens on class I MHC

DNA viruses:

  • EBV –> B cell lymphomas
  • HPV –> cervical carcinoma
  • HBV –> hepatocellular carcinoma

RNA viruses = HTLV-1 –> adult T cell leukemia/lymphoma (CD4 T cells)

**Tumors are relatively immunogenic because seen as foreign

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6
Q

Define Differentiation antigens

A

Differentiation antigens = tissue-sepcific antigens

  • -> aid in diagnosing certain tumors - reveal tissue of origin
  • -> E.G. pre-B cell tumors express CD10; T cell leukemias express CD4. CD8, TCR or IL-2 receptors
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7
Q

describe Anti-tumor antibodies

A

Difficult for immune system to respond to spontaneous tumors:

  • -> rarely cause inflammation - don’t elicit co-stimulatory molecules
  • -> many tumors don’t express unique antigenic peptides

Little evidence that natural antibodies stimulated by tumor antigens inhibit tumor growth ( not good)

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8
Q

Describe Cytotoxic T lymphocytes in response to cancer

A

Produced against carcinomas, sarcomas, and virus-induced tumors:

  • -> MOST effective against virus-induced tumors
  • -> tumor infiltrating lymphocytes (TIL’s) in solid tumors largely composed of anti-tumor CTL’s
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9
Q

Describe Natural killer cells in response to cancer

A

Lyse tumors of hematopoietic origin + those that are virus induced:

  • -> ADCC may be important with some tumors
  • -> activating signal = downregulation of class I MHC (which occurs in some tumors)
  • -> Inferferons, TNF-alpha, and IL-2 enhance NK cells lysis of tumor cells
  • -> Lymphokine-activated killer (LAK) cells – enhanced killing of various tumor cells types as well as broadened tumor recognition capability
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10
Q

Describe macrophages in response to cancer

A

Macrophages can kill tumor cells by ADCC or by release of TNF-alpha
–> TNF can directly lyse tumor cells possibly by producing free radicals or by causing hemorrhagic necrosis of the tumor blood vessel.

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11
Q

Describe Tumor evasion strategies

A

1) Lack of expression of MHC proteins (particularly class I MHC)
- - MHC proteins can’t bind tumor antigen –> no antigen presentation
- - Induce tolerance, I.e. no costimualtory molecules
2) Selection of poorly immunogenic variants by virtue of an effective anti-tumor immune response against the immunogenic tumor cells
3) Anti-tumor antibodies may act as blocking factors
4) antigen shed by tumor cells may bind to cell surface receptors
5) create an immunoprivileged site by encasing themselves in collagen

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12
Q

Describe radiotherapy in cancer treatment

A

Ionizing radiation –> destroys rapidly dividing cells

  • -> side effects include damage to bone marrow and intestinal mucosa, increase susceptibility to infection
  • -> may induce secondary tumor formation because of induced DNA mutation
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13
Q

Describe Chemotherapy in cancer treatment

A

Inhibites DNA replication, RNA transcription, or protein synthesis

  • -> side effects are problem; immunosuppression can be life-threatening
  • -> may induce secondary tumors
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14
Q

Describe the advantages of tumor immunotherapy

A
  • specifically tailor a response to the tumor
  • fewer side effects than nonspecific therapies
  • more effective against tumor metastasis
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15
Q

Define tumor vaccines

A
  • -> vaccinate with tumor cells treated to increase immunogenicity or dendritic cells that have been loaded with tumor antigens
  • -> melanoma antigens used in clinical studies to induce CTL’s
  • -> hepatitis B vaccine has decreased incidence of hepatocellular carcinoma.
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16
Q

Define antibody therapies

A

Antibodies to surface immunoglobulin of B cell lymphomas

  • -> cells lysis by ADCC or complement required to decrease tumor burden
  • -> outgrowth of tumor cell mutants are a problem

Antibodies directed against growth factor receptors:

  • Herceptin targets HER-2/neu growth factor receptor (overexpressed in 1/4 breast cancer)
    • blocks receptor/ligand interaction –> decrease expression of HER-2/neu
    • over-expression of HER-2/neu correlates with a poorer prognosis
17
Q

Define immunoconjugates

A

antibodies coupled to a toxic substance:

  • e.g. bacterial toxins, chemotherapeutic drugs, radioisotopes
  • must choose a tumor-specific antigen. cross-reactivity is a problem
  • conjugate must be endocytosed
  • F(ab’)2 fragments (no Fc regions) used to avoid non-specific binding

Bi-specific antibodies = genetically-engineered antibodies that recognize tumor antigens and immune system cells

18
Q

How do you purge bone marrow of tumor cells

A

in vitro purgin of bone marrow tumor cells by anti-tumor antibody and complement could provide a tumor-free source of bone marrow:
–> used with autologous bone marrow transplantation in B cell lymphoma patients that have received chemotherapy and radiation

19
Q

Define lymphokin-activated killer (LAK) cell therapy

A
  • Peripheral blood NK cells cultured in high dose IL-2 –> LAK cells
  • LAK cells reinfuesed into patient –> tumoricidal LAK cells kill tumor
  • most success with renal cell carcinoma and malignant melanoma
20
Q

Define tumor infilitrating lymphotyes (TIL) therapy

A
  • leukocytes from solid tumors cultured with IL-2 and given to patient
  • LAK cells and tumor-specific CTL’s are grown up in this technique
  • clinical trials are underway
21
Q

Define Cytokine therapy

A

IL-2 given to patients to generate LAK cells and activate CTL’s
- lots of severe side effects

TNF-alpha: powerful anti-tumor effects but too toxic at concentrations needed to eliminate tumor cells

IFN-alpha –> tumor antiproliferative effects, increase NK cell activity and increase class I MHC expression tumor cells

Transfection of cytokine genes into patient tumor cells –> immune stimulation while decreasing systemic side effects

Immunology II (8 decks)

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