Tumor Immunity Flashcards
TIL
Tumor invading lymphocytes. Often CD3+.
TIL experiment in mice
Showed that TILs from mice with early tumors could be injected into different tumor infected mice and shrink the tumor.
How are effector T cell responses generated against tumors?
Tumor cells with tumor antigens are digested by APCs. The antigens are presented on both MHC Class I and II to naive CD8+ and CD4+ T cells, along with necessary costimulators. These are activated, activate more CTL’s, which kill tumor cells expressing that antigen.
Why are APC’s needed to generate an effector T response to tumors?
Because tumor cells don’t present costimulators and don’t have high enough levels of antigen.
TAAs
Tumor associated antigens. They can be normal proteins that are usually silent in adults, they can be point mutated proteins, they can be overexpressed proteins, they can be oncogenic viral antigens. There are also non-mutated TAA’s like MUC and HER2/neu.
Why aren’t tumor cells rejected if effector cells against them exist?
Mechanisms working to prevent autoimmunity may stop effector response, tumor may secrete IL-10 or TGFß, loss of TAAs, loss of MHC, T regs suppress response.
If anti-tumor responses are made, can they be lost?
Yes. Thanks to T regs and mechanisms we don’t understand. As tumor size increases, loss of anti-tumor immunity occurs.
Do tumors grow in the absence of foxp3+ T regs?
No!
Passive immunotherapy
Therapies that include antibody infusion or T cell infusion to attack a tumor. No permanent change in patient immunity.
Active immunotherapy
Tumor vaccines that directly stimulate a patient’s immune response.
How do antibodies inhibit the growth of cancer cells?
Antibodies can induce cytotoxicity (NK cells, eosinophils), block tumor receptors for growth factors, and can deliver immunotoxins directly to a tumor.
Whole cell tumor vaccines
Inject patient with tumor cell that has been transfected with B7 or IL-2. In body, will encounter CD8+ T cells, stimulate them, causing clonal expansion of tumor reactive CTLs.
Adoptive T Cell immunotherapy
Take out part of tumor and isolate TILs in the presence of IL-2. Look for TILs that make high levels of interferon gamma. Culture and expand, inject back into patient.
Anti-CTLA 4 Therapy
Blocks CTLA 4 on T cells, prevents their downregulation.
