Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy
Cet article passe en revue les travaux récents sur l'identification de biomarqueurs permettant de prédire la réponse aux immunothérapies anti PD1 ou anti CTLA4 ainsi que la survenue d'effets indésirables liés à ces traitements
With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests. Here, we discuss biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria. The unique biology of the CTLA4 immune checkpoint, compared with PD1, requires a different approach to biomarker development. Mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade.
Nature Reviews Cancer , résumé, 2015