LAUSR

Abstract The development of immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway has significantly transformed the landscape of cancer treatment. However, resistance mechanisms such as alternative immune checkpoints, T-cell exhaustion, low tumor burden, and immunosuppressive cells in the tumor microenvironment can limit therapeutic efficacy. Recent research has highlighted the role of tumor-derived exosomes expressing PD-L1, which may contribute to resistance by locally and systemically suppressing immune responses. Inhibiting exosome secretion has shown promise in enhancing the effectiveness of anti-PD-1/PD-L1 therapies. The therapeutic potential of targeting exosomes to improve PD-1/PD-L1 inhibition is gaining attention, with preclinical studies showing encouraging results. Clinical trials are needed to evaluate the combination of exosome secretion inhibitors with existing checkpoint therapies and provide hope for patients with resistant cancers.