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A review by two of the field's leading trialists, written as checkpoint inhibitors reached a dozen cancers, explaining how CTLA-4 and PD-1 blockade work, why only some patients respond, and how resistance arises.
Ribas and Wolchok summarised the science and clinical results of checkpoint blockade at the point where PD-1 pathway antibodies had been approved across many cancers. They described CTLA-4 blockade as broadening the T cell repertoire and PD-1 blockade as reinvigorating exhausted T cells already in the tumour; reviewed the features of responding tumours, including mutational burden, pre-existing T cell infiltration and interferon-gamma signalling; and catalogued primary and acquired resistance mechanisms such as loss of antigen presentation and interferon signalling defects. They argued for rational combinations based on these mechanisms.
This is the standard overview of checkpoint immunotherapy for clinicians and scientists, tying together the trial results and the biology of response and resistance that guide today's combination trials.
Shares Tumeh 2014: PD-1 blockade works by releasing T cells already present at the tumour edge, Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Tumour mutational burden (TMB), Memorial Sloan Kettering Cancer Center.
Shares CTLA-4, Tumour mutational burden (TMB), PD-L1, PD-1.
Shares Jedd D. Wolchok, Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Immune-related adverse events (irAEs), CTLA-4.
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Immune checkpoint, PD-L1, Immune checkpoint inhibitors.
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, PD-L1, PD-1, Immune checkpoint inhibitors.
Shares CTLA-4, Memorial Sloan Kettering Cancer Center, PD-1, Immune checkpoint inhibitors.
Shares Jedd D. Wolchok, Immune-related adverse events (irAEs), CTLA-4, Memorial Sloan Kettering Cancer Center.
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, PD-L1, PD-1, Immune checkpoint inhibitors.