We discovered that tumor-derived exosome carrying 3′tiRNA-AlaCGC target fibroblasts, inducing a senescence-associated secretory phenotype (SASP) and activating the TGF-β/Smad3 pathway to increase Galectin-9 secretion; both SASP and Galectin-9 are known to induce CD8+T cell exhaustion. This evidence concerns the gene SMAD3 and neoplasm.