We introduce a novel multidimensional immune microenvironment reprogramming (IMER) framework that incorporates (i) longitudinal profiling of tumor-infiltrating lymphocytes (TILs), (ii) dynamic serum biomarker analysis [including high mobility group box 1 (HMGB1) and chemokine gradients], and (iii) spatial transcriptomic mapping of checkpoint ligand–receptor interactions. Here, HMGB1 is linked to neoplasm.