PRF1 and metastatic melanoma: Studies have demonstrated that CD8+ T cells primarily kill tumor cells by releasing cytotoxic factors such as perforin 1 (PRF1), granzyme A (GZMA), granzyme B (GZMB), granzyme H (GZMH).[41,42] Infiltration of CD8+ T lymphocytes into tumor tissue is considered a prerequisite for the successful treatment of metastatic melanoma with anti-PD-1, highlighting the critical role of CD8+ cytotoxic T lymphocytes in antitumor therapy.[30,43,44]