Immuno 19: Tumor Immunology Flashcards by Komron MacLean

Leukemia is basically a cancer involving what cells?

involving circulating cells

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lymphoma is basically a cancer involving what tissue?

solid lymphoid tissue

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myelomas are basically cancer involving what tissue?

bone marrow

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If a somatic cell undergoes a mutation and becomes cancerous, it will express mutated peptides via MHC class ____ that will be noticed by _____ cells that will signal for the cancer cell’s destruction.

MHC class I; CD8+ T cells (CTLs)

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Give two examples in which a tumor-associated antigen, rather than a tumor specific antigen (mutated peptide) would be expressed via MHC class II and recognized by CTLs for destruction.

1- Reactivation of embryonic genes not normally expressed in the differentiated cell by a tumor of embryonic cell origin.
2- Overexpression of normal self proteins by a tumor cell changes density of self-peptide presentation, allowing recognition by T cells. T cells will notice an abnormal increase in self-peptide expression and react to this as it would to cancer-specific peptides.

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Can normal (unmutated) cells express tumor-specific antigens?

Nope

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Briefly explain why somatic tumors are not contagious.

For the same reason transplanted tissue would be rejected by an allogeneic recipient (e.g. different HLA haplotypes), tumor cells would also be rejected and killed.

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What protein is mutated and type of cancer is this oncogene most commonly associated with?
HER2

growth factor receptor; Breast cancer

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What protein is mutated and type of cancer is this oncogene most commonly associated with?
B-RAF

intracellular signaling; melanoma

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What protein is mutated and type of cancer is this oncogene most commonly associated with?
MYC

transcription factor; neuroblastoma

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What protein is mutated and type of cancer is this oncogene most commonly associated with?
RAS

intracellular signaling; colorectal cancer

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What protein is mutated and type of cancer is this oncogene most commonly associated with?
Beta-catenin

intracellular signaling; array of tumor types

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What protein is mutated and type of cancer is this oncogene most commonly associated with?
VEGF

angiogenesis; metastatic colorectal cancer

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What protein is mutated and type of cancer is this tumor suppressor gene most commonly associated with?
APC

scaffolding protein (constitutive degradation of B-catenin); mutated in colorectal cancers

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What protein is mutated and type of cancer is this tumor suppressor gene most commonly associated with?
TP53

regulates cell division/apoptosis; mutated in lung cancers

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What protein is mutated and type of cancer is this tumor suppressor gene most commonly associated with?
RB

regulates cell division; mutated in retinoblastomas

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What protein is mutated and type of cancer is this tumor suppressor gene most commonly associated with?
CDKN2A

regulates cell division; mutated in melanomas

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What protein is mutated and type of cancer is this tumor suppressor gene most commonly associated with?
CDK4

regulates cell division; mutated in melanomas

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What protein is mutated and type of cancer is this tumor suppressor gene most commonly associated with?
p53

regulates cell division; mutations result in a wide array of tumors

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T/F: because tumor cells are rapidly dividing and genetically unstable cells, many mutations occur as the cells proliferate. Some of the mutations are in genes that have nothing to do with cell division or regulation of cell division. Any of these mutations could give rise to unique host determinants that could potentially be recognized by some of the CD8 T cells in the repertoire.

True

What are melanoma-antigen E (MAGE) proteins (also GAGE, BAGE, and RAGE) and why can they help the body recognize cancer?

MAGE proteins (and GAGE, BAGE, & RAGE) are encoded on genes that are expressed in the testes (and other immunoprivileged sites), but are normally not expressed in any other tissues. Because the testes are an immunoprivileged site, MAGE proteins are not available during T cell development and neg. selection in the thymus. Therefore, most people will not be tolerized to MAGE proteins. When MAGE expression in upregulated in a tumor cell, it can serve as a target for CTL response.

Altered cell surface ______ and ______ (tumor-specific antigens or tumor associated antigens) are expressed as abnormal forms and/or at elevated levels on tumors and thus can be diagnostic markers/therapy targets for anti-cancer drugs.

glycolipids and glycoproteins

MUC-1 (tumor-specific cell surface determinant) has tumor-specific carbohydrate and peptide epitopes recognized by both T cells as well as _______, making it a strong candidate for use in a tumor vaccine. MUC-1 is associated with this type of cancer:

antibodies; breast carcinoma

What are cell type-specific differentiation antigens and how can they help doctors determine at what time in a cell’s differentiation a neoplastic event occurred?

molecules that are normally expressed by a cell at different stages of differentiation of that cell type. A tumor cell will typically express antigens that were being expressed by the cell when the neoplastic event occurred.

Regarding cell type-specific differentiation antigens, if you found CD1 on a lymphocyte tumor's surface, you know the neoplastic event occurred when the cell was a:

thymocyte

Regarding cell type-specific differentiation antigens, if a T cell has undergone a neoplastic event at any point after reaching the thymic medulla, it will express CD3 and either ____ or _____ on its surface.

CD4 or CD8

Will the host produce tumor antigen-specific responses to cell type-specific differentiation antigens? Why or why not?

No, these are normally expressed proteins that were available during thymic neg. selection in the host.

Papillomavirus is associated with cancers of this tissue:

carcinoma of the uterine cervix

Hepatitis B virus is associated with cancers of this tissue:

Liver (hepatocellular carcinoma)

Epstein-Barr virus is associated with this type of cancer:

Burkitt's lymphoma (cancer of B cells) Nasopharyngeal carcinoma B-cell lymphoproliferative disease

Human T-cell leukemia virus type-1 (HTLV-1) is associated with this type of cancer:

Adult T-cell leukemia/lymphoma

HIV-1 is associated with this type of cancer:

Kaposi's sarcoma

Name 3 mechanisms (and 3 examples) by which tumor cells evade/overcome host immune responses.

1) some tumor cells produce cytokines (such as TGF-B) which create an immunosuppressive environment around the tumor 2) some tumors express Fas-ligand that can engage with Fas on immune cells, inducing them to undergo apoptosis 3) some tumors express PD-L1, a ligand for PD-1 expressed on effector T cells; PD-1 is a negative regulator of T cell effector function (similar to CTLA-4)

Describe 3 uses of humanized monoclonal antibodies (hmAbs) in treating cancer.

1) hmAbs can be used as ligand agonists or antagonists 2) hmAbs conjugated to toxins or radionucleotides (targeted killing of tumor cells) 3) hmABs can be used to target cells for killing by NK cells (ADCC) and via the complement cascade (MAC)

Sweatman review! Here's a hmAb drug, name its target antigen and the cancers treated: Rituximab

CD20; Non-Hodgkin's lymphoma

Sweatman review! Here's a hmAb drug, name its target antigen and the cancers treated: Trastuxumab

HER2/neu protein; Breast cancer

Sweatman review! Here's a hmAb drug, name its target antigen and the cancers treated: Alemtuzumab

CD52; Chronic lymphocytic leukemia

Sweatman review! Here's a hmAb drug, name its target antigen and the cancers treated: Cetruximab

Epidermal growth factor receptor (EGFR); colorectal cancer & head and neck cancer

Sweatman review! Here's a hmAb drug, name its target antigen and the cancers treated: Panitumumab

EGFR; colorectal cancer

Sweatman review! Here's a hmAb drug, name its target antigen and the cancers treated: Bevacizumab

VEGF; colorectal cancer & non-small cell lung cancer

How do Ab-toxin conjugates kill tumor cells, basically?

Antibody specific to tumor cell determinant binds to tumor cell and the Ab-toxin complex is endocytosed at which point the toxin induces the death of the cell by various mechanisms.

How do Ab-radionucleotide conjugates kill tumor cells, basically?

Antibody specific to tumor cell determinants binds to tumor cell at which point the attached radionucleotide irradiates the tumor cell, causing double-stranded DNA breaks, killing the cell.

Name two antagonistic Abs of the Her2 receptor.

Trastuzumab | Pertuzumab

Name two antagonistic Abs of EGFR.

Cetuximab | Panitumumab

Name the mAb-chemo conjugation that is used for pre-treated HER2-positive breast cancers.

T-DM1

Name the mAb that binds CTLA-4, blocking its interaction with B7 of APC so that CD28 can bind B7 for the 2nd signal of activation of T cells.

Ipilimumab

What is a deviant mechanism that tumor cells use to prevent CTL mediated killing of tumors that involves binding PD-1 receptors on T cells that interfere with their effector cell function. Name the 1 anti-PD-L1 mAb and the 2 anti-PD-1 mAb used to treat cancer.

secretion of PD-L1 (ligand for PD-1) Anti-PD-L1: MPDL3280A Anti-PD-1: Nivolumab and Lambrolizumab

Describe the concept of Bispecific Abs.

An Ab that with one arm, binds a receptor on a tumor cell, and with the other, binds a receptor on an effector cell, such as a CTLs. This effectively targets the CTL to the tumor cell for destruction.

Explain the concept of the chimeric antigen receptor and how it is used to fight cancer.

Instead of targeting CTLs to tumors using TCRs and tumor-specific or tumor-associated peptide determinants, as God intended, we genetically modify T cells to express a protein specific for Abs that are specific for tumors. Thus, a bispecific Ab can be used to link a chimeric T cell to the target tumor. SCIENCE IS THE NEW GOD