Immune checkpoint blockade(ICB)with antibodies interfering with cytotoxic T lymphocyte antigen 4(CTLA-4)and the programmed cell death 1(PD-1)protein tremendously revolutionized therapy for advanced cancer.Nevertheless,the activity of such agents(ipilimumab and nivolumab)is limited to a 10–45%response rate in the context of unselected populations with advanced solid tumors.Several common cancer types have demonstrated a very low frequency of response(breast,prostate and colon cancers),and heterogeneous responses have been observed between distinct tumors within the same patient.Challenges to broad clinical applicability include identifying patients most likely to benefit from checkpoint inhibitors and overcoming resistance to ICB.The immune response is a dynamic and constantly evolving process due primarily to patient-dependent factors,including genetic and tumor microenvironment(TME)features,and secondarily to treatment interventions.
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