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For cancer treatment, immunotherapy is becoming the standard treatment for many types of cancer and is often combined with chemotherapy. Although chemotherapeutic agents are often reported to have adverse effects, including immunosuppression, they can also play a positive role in immunotherapy by directly stimulating the immune system. This has been demonstrated in preclinical and clinical studies in the past decades. Chemotherapeutics can activate immune cells through different immune receptors and signaling pathways, depending on their chemical structure and formulation. In this review, the direct immunoactivation effects of chemotherapeutics and the possible mechanisms behind these effects are summarized and discussed. 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