CD81 and neoplasm: Therefore, a series of complementary markers may be helpful alongside ExoPD-L1, such as: exosomal CD63/CD9/CD81, which confirm exosomal purity; ExoPD-L1 that reflects T cell exhaustion or a suppressed immune status; immune checkpoints (ICIs) such as exosomal CTLA-4, TIM-3, and LAG-3, which indicate tumor immune evasion and adaptive resistance; other markers for inflammation, proliferation, and tumor angiogenesis, such as miRNAs, EGFR, HER2, KRAS mutations, lack of MHC I/MHC II; and the cytokine profiles that can highlight a TME with an inflammatory status often involved in resistance to ICIs.