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While chemotherapeutic agents were long solely associated with immunosuppression, clinical data demonstrate that the combination of some chemotherapies with immunomodulators can be beneficial against cancer. Defining combinations featuring optimal anticancer activity along with minimal toxicity remains however a major challenge. Clinical evidence suggests that immune responses in patients treated with combination therapies are associated with progression-free survival. Progress in understanding the mechanisms responsible for anticancer immune responses following chemotherapy administration facilitated the translation of relevant chemoimmunotherapy combinations in the clinic.