CAFs secreting TGF-β and C-X-C motif chemokine ligand 12 (CXCL12) to form fibrotic barriers blocking T cell migration (44, 61, 62) (5); metabolic disorders in hypoxic tissues and lactate accumulation causing acidification that suppresses T cell function and promotes exhaustion (9, 60, 63) (6); in MSS tumors, DNA hypermethylation silencing C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10 expression, blocking T cell recruitment (19, 59, 64). Here, CXCL12 is linked to metabolic disease.