Tumor Immunology Flashcards by Bryan Edwards

Cause of Cancer

Accumulated mutations in genes that ocntrol cell growth and death

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What do carcinogens do?

Induce mutations into DNA

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T or F. Typically a single genetic abnormality will lead to cancer.

F. Accumulations of mutations tend to lead to cancer cell development

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Why are some individuals more prone to develop cancer (even with comparable lifestyles to others)

Inherited mutations in genes that control DNA stability or growth (Ex. BRCA1, BRCA2)

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Size of average tumor when first visible on Xray?

At death of patient?

10^8

10^12

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Describe characteristics of a malignant tumor

Malignant cells are more aggressive in growth

Spread to nearby tissues/different organs through lymph and BV

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What is a carcinoma?

Epithelial Cell Tumor

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What is a leukemia?

Tumors of circulating cells

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What is a lymphoma?

Solid tumor in lymph node

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What is a myeloma?

Tumor of Bone marrow cells

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What is a sarcoma?

Tumor of Connective Tissue Cells

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Viruses associated with human cancers?

Papillomavirus (Uterine Cervix)
Hepatitis B Virus (Liver Cancer)
Epstein Barr Virus (Burkitt's Lymphoma, B-Cell 
          Lymphoproliferative disease)
HTLV-1  (Adult T-cell Leukemia)
HIV-1  (Kaposi's Sarcoma)

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How might viruses induce proliferation?

Blocking P53 and Rb

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Can tumor cells grow in another person?

Usually, No.

Yes if the other person is the same MHC haplotype

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Four immune cells responsible for finding tumors

CD4, CD8, NK cells, and B cells

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What do T and B cells target in cancer?

Tumor antigens that are differentially expressed by tumor cells and normal cells

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What are tumor specific antigens?

Mutant peptide presented in cancer cells that is distinct from normal healthy cells

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What are tumor-associated antigens?

Antigens brought about by reactivation of embryonic genes

2. 10X or more overexpression of self proteins

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Give an important example of a tumor-specific shared antigen

Melanoma antigen - 1

Found on melanomas and other transformed cells

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Give an important example of a tissue-specific antigen found on normal and transformed cells.

Tyrosinase

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Give two examples of Oncofetal antigens

Carcinoembryonic Antigen (CEA) -- Colon Cancer
Alpha-fetoprotein -- Liver and testis cancer

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Give two examples of differentiation antigens

Common acute lymphoblastic leukemia antigen (CALLA/CD10) – Acute Lymphoblastic Leukemia

PSA – Prostate Cancer

Give an example of abnormal post-translational modification leading to cancer

Underglycosylation of Mucin caused by MUC-1 – Breast and Pancreas

Give an example of a cancer with a mutated oncogene or tumor suppressor antigen.

Cyclin-dependent kinase 4 – Melanoma

MART2. Name the disease, HLA restriction.

Melanoma. A1

ME1. Name the disease, HLA restriction.

Non-small cell lung carcinoma. A2

p53. Name the disease, HLA restriction.

Head and Neck Squamous Cell Carcinoma | A2

KIA0205. Name the disease, HLA restriction.

Bladder | B44

Trisephosphate isomerase. Name the disease, HLA restriction.

Melanoma | DR1

BCR-ABL Fusion Protein. Name the disease, HLA restriction.

CML | DR4, B8, A2

Five cells involved in cell mediated tumor response.. | What do they do?

``` CD4 -- Control other cells by cytokines CD8 -- direct lysis NK cells -- direct lysis gd T cells -- cytokines and lysis Eosinophils -- Degranulation ```

Two important roles of Antibodies in tumoral response?

Facilitate NK cell mediated lysis of tumor cells | Activate complement reaction

How does the body deal with tumors that lack MHC1 expression?

NK cells kill them

How do dendritic cells present to both CD4 and CD8 T cells?

Dying tumor cell is taken in by both endocytosis and membrane fusion

Give six methods Tumors can use to evade immune response

1. Outgrowth of antigen-negative variants 2. Loss/Reduction of MHC proteins 3. Secretion of Immunosuppressive cytokines 4. Induction of CTL apoptosis via FAS ligand 5. Lack of Co-stimulatory signals 6. Soluble tumor antigens (to induce tolerance)

How common is removal of MHC 1 expression

30-50% of tumors

Examples of immuno suppressive cytokines that might be secreted by tumors

TGF-beta TH2 cytokines (IL10)

How might tumor cells that ditch their MHC1 continue to evade NK Cells?

Shedding of MHC Class I related Chain (MIC), a ligand of NKG2D (NK activating receptor)

Describe MIC in tumor biology.

Normally elevated expression in tumor cells. NKG2D on T cells and T cells bind it --> Kill Tumor By cleaving MIC from surface, soluble can bind lymphocytes and not involve the tumor Tumor can now survive and proliferate

Actions of TGF-beta that support tumor growth?

Induce Tregs (inhibit CTL, release more TGF and IL-10) Inhibit CTL Inhibit TH1

Five types of immunotherapy

``` Non-specific stimulation Active Immunization with tumor antigens Cytokine therapy Adoptive cellular monotherapy Anti-tumor antibodies (coupled to cytotoxins/radioiso) ```

Example of Non-specific adjuvant therapy.

Injecting killed mycobacterium (BCG) into bladder to treat superficial bladder cancer

How might non-specific adjuvant therapy work?

Bacterial products increase T cell Response | Induce co-stimulation molecules and MHC molecules of APCs

How can antibodies against tumor antigens be used?

Immunotoxins and induction of ADCC by NK cells

Explain what is meant by tumor vaccines.

Tumors taken at surgery are manipulated ex vivo -- used as vaccine. Made to express B7, GM-CSF, or IL12 in tumor cell Also...tumor antigens can be used (ex. CEA)

What is dendritic cell therapy?

Patient Dendritic cells are isolated and loaded with tumor antigen in vitro. Cells are injected into patients to boost anti-tumor T cell response

What happens in T cell therapy?

Patients T cells are activated in vitro with tumor antigens and cytokines, inject back into patients

What is Sipuleucel-T/Provenge?

A cancer vaccine for prostate cancer Patient Blood->DC + Fusion protein with PAP and GM-CSF-> infusion into patient

Explain monoclonal antibody treatment with Rituxan

Anti-CD20 antibodies to target non-Hodgkin's lymphoma

Name two types of radiolabeled antibodies used to detect cancer

Oncoscint -- Colorectal + Ovarian | Prostascint -- Prostate

Explain how antigen-GM-CSF fusion proteins work?

Patient Monocytes are cultured with fusion protein of GM-CSF and PAP Induces DC development, PAP presented on MHCII Activated cells infused into patient, present to T cells

How does Anti-CTLA4 antibody work in cancer treatment?

If B7 binds CD28, activation If B7 binds CTLA4, anergy Antibody blocks CTLA4, so any TCR binding will result in activation

Explain chimeric antigen receptor-transduced T cells

Chimeric receptor is added to T cells by R-Trans activity T cells can now bind with Ab domain T cell killing power with B cell targeting skills