Interestingly, all granzymes except GzmA were induced by Mn2+ treatment, consistent with previous works, including multicenter clinical studies, demonstrating that GzmA is not important in T cell or natural killer (NK) cell-mediated cytotoxicity, instead acts as a pro-inflammatory cytokine contributing to cancer development.35,36 The increase of granzyme B and perforin producing CD8+ TILs was verified by flow cytometry (Fig. 2g). Here, PRF1 is linked to cancer.