HMGB1 and neoplasm: Finally, TANs mediate immune evasion by depleting nutrients like glucose [80], releasing immunosuppressive metabolites such as lactic acid [81] and PGE2 [82], upregulating PD-L1 in response to tumor-derived signals such as TNF-α, GM-CSF, high mobility group box 1 (HMGB1), IL-6, and CCL20 [86,87,88,89,90,91,92], and inducing immunosuppressive cytokines including IL-10 and interleukin-1 beta (IL-1β) [15,63,83].