PD-L1 promotes tumor metastasis by regulating the infiltration of FGFBP2(+)Tm cells in colorectal cancer

Abstract Tumor infiltrating lymphocytes largely determined tumorigenesis and progression. We found PD-L1 can inhibit the infiltration of memory T cells in vivo and in vitro by reducing the secretion of CXCL9,CXCL10 in colorectal cancer. Clinically, patients with high PD-L1 expression had few memory T cells infiltration, resulting in a higher incidence of tumor metastasis. Furthermore, single-cell sequencing revealed that PD-L1 mainly inhibited the tissue infiltration of a specific Tm cell subset characterized by the expression of FGFBP2 gene. To clarify the distribution of FGFBP2(+)Tm cells, peripheral blood, lymph nodes, colon polyps, primary tumor, and liver metastases samples were collected. As the tumor progressed, the infiltration of FGFBP2(+) memory T cells gradually increased and accumulated in liver metastases. FGFBP2(+) memory T cells were closely correlated with the distribution of CD31 and positively correlated with the neovascularization density and metastatic nodules. By comparing the transcriptome differences between metastatic and non-metastatic lymph nodes, it was revealed that the expression of FGFBP2 and FGF19 were significantly increased in metastatic lymph nodes. Mechanistically, FGF19, the binding factor of FGFBP2 can induce inflammatory cancer-associated fibroblasts resulting in liver metastasis. Therefore, the elevated FGFBP2(+) memory T cells can promote liver metastasis in colorectal cancer. One Sentence Summary: PD-L1 can inhibit the infiltration of memory T cells, and increased FGFBP2(+)Tm cells can promote tumor metastasis