20. Tumor Immunology

Question 1

what is the conclusion from the following evidence supporting immunosurveillance of cancer?

lymphocytic infiltrates around some tumors and enlargement of draining lymph nodes correlate w/better prognosis

Answer 1

immune responses against tumors inhibit tumor growth

Question 2

what is the conclusion from the following evidence supporting immunosurveillance of cancer?

transplants of a tumor are rejected by animals, and more rapidly if the animals have been previously exposed to that tumor; immunity to tumor transplants can be transferred by lymphocytes from a tumor-bearing animal

Answer 2

tumor rejection shows features of adaptive immunity (SPECIFICITY, MEMORY) and is mediated by lymphocytes

Question 3

what is the conclusion from the following evidence supporting immunosurveillance of cancer?

immunodeficient indivs have increased incidence of some types of tumors.

Answer 3

immune system protects vs the growth of tumors

Question 4

what is the conclusion from the following evidence supporting immunosurveillance of cancer?

therapeutic blockade of inhibitor receptors like PD-1 and CTLA-4 leads to tumor remission

Answer 4

tumors evade immune surveillance in part by activating inhibitory receptors on T cells

Question 5

TSA vs TAA

Answer 5

TSA: uniwue to tumor cells and not expressed on normal cells - responsible for rejection of the tumor

TAA: expressed by tumor cells and are normal cells (abberrantly expressed or over expressed) - most common

Question 6

TAA or TSA? various mutant proteins in carcinogen or radiation-induced tumors?

Answer 6

TSA

Question 7

TAA or TSA? oncogene products: mutated Ras, Bcr/Abl fusion proteins or tumor suppressor gene products: mutated p53

Answer 7

TAA

Question 8

TAA or TSA? tyrosine, gp100, cancer/testis antigens in various tumors (melanoma)

Answer 8

TAA

Question 9

TAA or TSA? HPV E6, E7 proteins in cervical carcinoma; EBNA proteins in EBV-induced lymphomas?

Answer 9

TSA

Question 10

what is necessary for a CD8+ cell to respond to a tumor antigen directly?

Answer 10

cross priming

Question 11

HSP and IFN-a can be considered what types of signals in a tumor cell?

Answer 11

DAMPs - SOS

Question 12

what receptor on NK cells is responsible for ADCC?

Answer 12

low-affinity FcgammaRIII

Question 13

what are the outcomes of immunoediting?

Answer 13

1. Elimination of the cancer
2. cancer Equilibrium
3. tumor Escape (thanks to immunosuppressive factors)

Question 14

interactions b/w tumor and immune cells cause tumor immune tolerance through what mechanisms?

Answer 14

1. ignorance: lack of tumor recognition by immune cells due to loss of tumor Ag and/or MHC expression on tumor (or defect in antigen presentation machinery like TAP-1 downregulation)
2. deletion; apoptosis of immune cells triggered by tumor-derived pro-apoptotic factors (eg FasL)
3. anergy; unresponsive state of immune cells due to lack of co-stimulatory signals
4. suppression; passive inhibition of tumor-reactive immune cells by suppressive factors (like IDO) and cells (eg Treg and MDSC)

Question 15

eg of passive immunity?

Answer 15

transfer of tumor-specific T cells or antibodies into patients

Question 16

eg of active immunity?

Answer 16

DC vaccines

blockade of T cell inhibitory molecs (CTLA4 or PD-1)

Question 17

steps to find new tumor antigens?

Answer 17

1. generate map or tumor-specific mutations (DNAseq: exome, whole genome)
2. determine which mutated genes are expressed (RNA seq)
3. predict epitopes for each mutation per HLA-allele in silico (anti-genome)
4. screen for T cell recognition of mutated epitope

Question 18

cetuximab

Answer 18

anti-EGFR mAb, approved for metastatic colorectal cancer and head/neck cancer

Question 19

trastuzumab

Answer 19

anti-Her2/neu receptor mAb. Approved for metastatic breast cancer

Question 20

rituximab

Answer 20

anti-CD20 mAb. Approved for B-cell lymphoma