Tumor Immunology Flashcards by Savannah Smith

tumor antigens

mutated protein
normal cells do NOT express these antigens
not available during neg. selection: loaded onto MHC class I and presented to CTLs

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tumor-associated antigens

un-mutated protein that is encoded in germ-line DNA of a cell whose level of expression has been dramatically altered by a neoplastic event
1. embryonic cells not available in T cell development
MHC class I presents to T cells
2. increased expression of normal self protein
increased density can lead to recognition by effector CTLs

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proto-oncogenes

when mutated and activated: transform normal cell into a tumor cell

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tumor suppressor genes

gene that encodes a protein that exerts control on cell growth rates

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oncogenic viruses

express antigens that can serve as tumor antigens

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Adaptations of tumors that enable them to avoid immune detection or effector function

down-regulation of MHC class I

2. down regulation of T cell activation or effector function: expression of CTLA-4, TGF-beta, Fas-ligand, or PDL-1

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bispecific Ab

recombinant with two arms
1. specific for CD3
2. specific for tumor antigen
recruits CD8 T cells to tumor
NOT a specific antigen activation: any T cell can be recruited
close contact causes degranulation rather than MHC and B7

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CAR

chimeric antigen receptor
CTL with B cell receptor (heavy, light, and CD3 zeta chain)
CD3 zeta chain: causes intracellular signaling ot occur

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carcinoma

cancer of epithelial cells

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sarcoma

cancer of CT or non epithelial cells

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leukemia

cancer of circulating cells of immune system

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lymphomas

cancer of immune system involving solid lymphoid tumors

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myelomas

cancer of immune system involving bone marrow

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What is the effector mechanism our immune system sometimes has against tumor cells?

CTL

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syngenic tumor transplantation

can transfer tumor from one mouse to another if they have matching MHC haplotypes
proves CTL resonse

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allogenic tumor transplantation

can NOT transfer tumor between mice with mismatching MHC haplotypes
proves CTL response

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HER2

oncogene: GF receptor

breast cancer

B-RAF

oncogene: intracellular signal

melanoma

MYC

oncogene: TF

neuroblastoma

RAS

oncogene: intracellular signal

colorectal cancer

B-catenin

oncogene: intracellular signal

various cancers

VEGF

oncogene: angiogenesis

colorectal cancer

APC

tumor suppressor: scaffolding protein

colorectal cancer

TP53

tumor suppressor: regulates cell division

lung cancer

tumor suppressor: regulates cell division | melanoma

CDKN2A

tumor suppressor: regulates cell division | melanoma

p53

tumor suppressor: regulates cell division | various cancers

MAGE, GAGE, BAGE, RAGE

target of CTL-mediated killing when expressed outside of testes (immunoprivileged: not available during T cell development)

oncofetal antigens

genes normally only expressed during embryonic development that are expressed in a tumor NOT available for B and T cell negative selection

MUC-1

mucin found on many breast carcinomas | tumor specific carbohydrate and peptide epitopes: induces both antibody and T cell response

examples of abnormal forms or elevated levels of glycolipids and glycoproteins that can be diagnostic for cancers

gangliosides, blood group antigens, mucins

CA-125

mucin found in ovarian carcinomas

CA-19-9

mucin found in ovarian carcinomas

cell type specific differentiation antigens

normally expressed by a cell at different stages of differentiation of that cell type; tumor cell will typically express antigen that were being expressed by the cell when neoplastic event occurred ex: CD20, CD1, CD3, CD4, CD8 normally recognized proteins that were available during thymic selection: no T cells specific for them

TGF-beta

immunosuppressive environment around the tumor

Fas-ligand

engage with Fas on immune cells and induce apoptosis

PD-L1

ligand for PD-1 on effector T cells down regulation of function protection from CTLs if expressed

How can tumors evade the immune system?

1. defects in expression of MHC class I: Evade CTL but increase NK killing 2. TGF-beta 3. Fas-Ligand 4. PD-L1 5. CTLA-4

conjugated Ab

tumor-antigen specific MAb delivers toxin, drug or radio nucleotide to tumor

CTLA-4

on naive T cells and Tregs binds B7, preventing CD28 from binding causes T reg to secrete TGF-beta, preventing T cell activation

blinatumomab

biphasic Ab anti-CD3 arm (T cell) and anti-C19 arm (tumor antigen) Tx: B cell lymphoma