Therapeutic potential of natural products in cancer immunotherapy: Advances and challenges

Immunotherapy has emerged as a clinically pivotal approach in cancer treatment, but its application remains limited to a small subset of patients. Current data indicate that less than 10% of patients respond to mono-immunotherapy, and acquired resistance further restricts its efficacy. Elucidating the mechanisms of non-response and developing strategies to increase therapeutic sensitivity are critical for advancing immunotherapy. Natural products have long played a vital role in anticancer drug discovery because of their structural diversity and demonstrated biological activities. In this review, we provide a systematic classification of immunotherapies and summarize mechanisms associated with treatment resistance. We highlight promising natural products shown to enhance immunotherapeutic efficacy through the modulation of immune resistance pathways and discuss translational challenges hindering the clinical application of natural products, proposing their potential as synergistic agents to overcome current limitations in cancer immunotherapy. Harnessing natural products may thus open new avenues to overcome immune resistance and broaden the therapeutic effects of cancer immunotherapy.