The proposed mechanism of action for NIR-PIT combined with ICIs in malignant tumors, presented in Figure 1, is as follows: NIR-PIT results in disruption of cancer cell membranes, which release signals and molecules such as heat shock proteins 70 (Hsp70) and 90 (Hsp90), calreticulin (CRT), adenosine triphosphate (ATP), and high-mobility group box 1 (HMGB1) protein, activating naϊve dendritic cells in the vicinity and in the TME, which will mature by ingesting cancer-specific antigens (Ags) freshly released by dying tumor cells. This evidence concerns the gene HMGB1 and neoplasm.