tumor immunity and immunotherapy

Question 1

how does the immune system recognize and kill tumor cells?

Answer 1

• neoplastic transformation => formation of new tumor associated antigens (TAA)
• adaptive immune response: T cells recognize TAA => direct killing of tumor cells
• innate immune response: NK cells recognize lack of MHC class I (if KIR receptor doesn’t bind MHC class I) => direct killing or bind Fc portion of antibodies bound to tumor antigens and killing via ADCC

Question 2

how do tumors evade the immune system?

Answer 2

• downregulate TAA
• decrease MHC expression (so less antigen presentation)
• suppression of T cells response through production of anti-inflammatory cytokines (TGF-B) or expression of inhibitory cell surface molecules (PDL1 to interact with T cell PD1)

Question 3

what are some examples of cancer immunotherapy strategies?

Answer 3

• activation of anti-tumor T cells
• antibodies against PD1/PDL1 block their interaction => inhibit inhibition of T cell activation
• checkpoint immunotherapy: antibodies that block CTLA-4 => inhibit inhibition of T cell activation
• antibodies that bind to tumor antigens
• anti-CD20 (rituximab)
• chimeric antigen T cell receptor therapy (CAR-T): modify patient’s T cells to express antibody again CD19 (B cells) fused to TCR => B cell recognition -> killing
• vaccines against tumors or cancer causing infection

Question 4

what are some therapeutic approaches to break tolerance to tumor cells?

Answer 4

• enhance the T cell response by increasing pro-inflammatory cytokines (IFN, IL-2)
• mab’s against tumor antigens or proteins that block the immune response; labelled antibodies that could deliver a drug
• vaccines to enhance tumor antigen processing
• gene/cell tx