Tumor Immunology

Question 1

Give evidence for the immune surveillance theory.

Answer 1

1. People with immunodeficiencies, particularly of T cells, have a higher incidence of tumors. 2. Activated T cells that recognize tumor-associated antigens can easily be identified. 3. A small percentage of tumors, mainly melanomas and some lymphomas, spontaneously regress, presumably due to an immunologic response.

Question 2

What are clonal antigens?

Answer 2

antigens expressed uniquely on the malignant clone, sch as surface Ig in B cell malignancies or TCR in T cell malignancies

Question 2

How do NK cells kill tumor cells?

Answer 2

attack cells with less MHC1 via granules they release

Question 3

How come CTLs can surround a tumor but not kill it?

Answer 3

they have 2 surface checkpoint inhibitors receptors, CTLA-4 and PD-1, that are downregulated by the tumor

Question 3

What are tumor specific antigens (TSA)?

Answer 3

antigens that only occur in one individual’s tumor

Question 4

How do macs and neutrophils kill tumor cells?

Answer 4

activated by foreign tumor product

Question 5

Name some tumor escape mechanisms.

Answer 5

1. modify their TAMs 2. make immunosuppressive factors like TGFbeta 3. make macs become immunosuppressive 4. shed TAMs to decoy CTLs 5. reduce their MHC1 expression

Question 5

What is oncofetal antigen?

Answer 5

normal fetal tissue that shouldn’t be made in adults, such as carcinoembryonic antigen (CEA) in colon CA

Question 7

How are DCs tumorcidal?

Answer 7

directly or via ADCC

Question 9

What are the 3 stages of immunoediting?

Answer 9

1. Elimination 2. Equilibrium 3. Escape

Question 10

What is innocent bystander killing?

Answer 10

inject BCG (the tuberculosis vaccine) directly into the tumor. A ferocious delayed-type hypersensitivity reaction to BCG ensues, and the tumor cells are killed as innocent bystanders.

Question 11

What is a differentiation antigen?

Answer 11

a lineage-specific TAA that is overexpressed in certain tumors, like Her-2 in breast cancer, that indicate malignancy

Question 12

How does antibody and complement work to kill tumor cells?

Answer 12

they don’t work very well

Question 13

How do CTLs kill tumor cells?

Answer 13

by inducing apoptosis via either perforin or Fas-mediated pathways; also secrete IFN; CD8+

Question 14

Why can’t CEA be used as a routine CA test?

Answer 14

too many false positives

Question 15

What are tumor-associated antigens (TAA)?

Answer 15

normal cell markers that are overexpressed or abnormally expressed by tumors

Question 17

Name 2 surface checkpoint inhibitor receptors that CTLs have.

Answer 17

CTLA-4 and PD-1

Question 18

How do Th1 cells kill tumor cells?

Answer 18

CD4+ cells make lymphokines and attract angry M1 macs