Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1/PD-L1 (Programmed Death 1/Programmed Death-Ligand 1) axis, have modified the management of many types of cancer over the last 10 years. However, both intrinsic and acquired resistance are major clinical issues with these therapies, and only a few patients are cured by ICI monotherapy. To overcome resistance, the concept of combining ICIs with other therapies is emerging and supported by many preclinical trials. Besides associations of ICIs with chemotherapy or radiotherapy, now used in clinical practice, some targeted therapies have also been reported to influence immune response of patients against cancer cells, thus showing potential synergy with ICIs. In this review, we describe the preclinical and clinical advances to date in the use of these combination strategies.

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