Discussion

Immune mediated therapies for cancer (IMT-C), such as anti-CTLA-4 and anti-PD-1/PD-L1, are showing significant promise in the treatment of solid tumors. However, although these treatments can show significant overall benefit, a subset of patients fails to respond. It is believed that activity in these patients is limited by a lack of immune priming or by immunosuppression. Combination with standard of care therapies (such as, chemo- and radiotherapy), molecular targeted therapies and or other IMT-Cs, has the potential to overcome these hurdles to response and maximize patient benefit. In order to select the best combination partners, a greater understanding is needed as to how other therapies affect the immune system both directly, through effects on leukocytes, and indirectly, through effects on tumor immunogenicity and induction of tumor cell death. Presented is a preclinical systematic approach taken towards examining the effects of combining the above modalities with IMT-Cs.