Overview of the immune response to tumors and immunotherapy

Question 1

What are some general categories of tumor antigens?

Answer 1

mutated proteins, viral antigens expressed by virus associated tumors, cancer/testis antigens, over expression or abnormal expression of cellular proteins, differentiation antigens

Question 2

What is the biggest challenge when trying to eliminate a tumor?

Answer 2

the tumor is self (created by cells from the organism), and we are tolerant to self

Question 3

What are the important innate cellular immune response to tumor cells?

Answer 3

NK cells and macrophages

Question 4

How do NK cells recognize cells to kill by?

Answer 4

decreased MHC I presentation, the binding of stress proteins, ADCC (bound antibody to tumor)

Question 5

What are M1 macrophages activated by?

Answer 5

interferon gamma

Question 6

How do macrophages kill tumor cells?

Answer 6

via cytokines, lysosomal enzymes, and nitric oxide and oxide radicals

Question 7

What are important adaptive cellular immune response mechanisms that contribute to killing tumor cells?

Answer 7

host APCs take up tumor cells to present to MHC I and II, CTLs, and T-helper 1 cytokines

Question 8

What is the role of antibodies in killing tumor cells?

Answer 8

they do not actually do the killing, but they mark the cell to be killed

Question 9

What are the three ways that tumor cells evade being detected by the immune system?

Answer 9

tolerance, inhibition of T cell activation, lack of T cell recognition of the tumor

Question 10

How do tumor cells inhibit T cell activation?

Answer 10

with PDL1

Question 11

How do monoclonal antibodies work?

Answer 11

monoclonal antibodies bind to PD1 or PDL1 to block the inhibition of T cell activation and allow CTLs to kill

Question 12

What type of ‘vaccine’ is the canine melanoma vaccine?

Answer 12

xenogeneic DNA vaccine

Question 13

What is the tumor antigen that canine melanoma vaccine targets?

Answer 13

tyrosinase

Question 14

How does the canine melanoma vaccine work?

Answer 14

the human tyrosinase gene is inserted into a bacterial expression plasmid, the tyrosinase protein is made and presented on both MHC I and MHC II which are then recognized by CTLs and TH cells as foreign because the trosinase is human, and there is enough simularity that they attack both the human and canine tyrosinase in the dog