Trogocytosis in cancer immunity and cellular immunotherapy: mechanisms, therapeutic challenges, and translational opportunities

Trogocytosis has emerged as a critical regulator of tumor immunity and cancer immunotherapy. This contact-dependent process enables the transfer of membrane fragments and associated molecules between interacting cells, thereby reshaping cellular phenotype, signaling, and immune function within the tumor microenvironment (TME). Recent evidence demonstrates that trogocytosis exerts context-dependent effects in cancer, functioning as both a mechanism of antitumor immunity and a driver of immune evasion and therapeutic resistance. Immune cells can utilize trogocytosis to mediate tumor cell killing through trogoptosis, enhance antigen presentation, and promote immune priming. Conversely, malignant cells exploit this process to acquire immunosuppressive molecules, downregulate tumor-associated antigens, induce exhaustion and fratricide of effector lymphocytes, and establish an immunosuppressive niche that favors tumor progression. In this review, we comprehensively discuss the mechanistic basis of trogocytosis in innate and adaptive immune responses against cancer and highlight its role in tumor progression, immune escape, and modulation of the TME. We further examine the implications of trogocytosis in cellular immunotherapies, particularly chimeric antigen receptor (CAR)-engineered immune cells and dendritic cell (DC) vaccination. Finally, we summarize emerging therapeutic strategies aimed at modulating trogocytosis to improve the efficacy and durability of cancer immunotherapies. A deeper understanding of trogocytosis and its context-specific functions may support the development of safer and more effective next-generation immunotherapeutic approaches.