Furthermore, we discovered that tumor-derived exosome carrying 3′tiRNA-AlaCGC target fibroblasts to induce a senescence-associated secretory phenotype (SASP) by inhibiting FOXO3, and activating the TGF-β/Smad3 pathway, thereby increasing Galectin-9 secretion; both SASP and Galectin-9 induce synthetically dysfunction of cytotoxic CD8+ T cells. Here, SMAD3 is linked to neoplasm.