In CRC, the major efferent signals for epithelial cells included MIF, APP and MK signals, while for monocyte-macrophages included MHC-II, CXCL and SPP1 signals, which the high expression of SPP1 in macrophages having strong senescence-associated secretory phenotype (SASP) features (38). The gene discussed is SPP1; the disease is colorectal carcinoma.