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

Abstract

Tumor-infiltrating lymphocytes can influence tumorigenesis and progression. We found PD-L1 can inhibit the infiltration of memory T (Tm) cells in vivo and in vitro by reducing the secretion of CXCL9, CXCL10 in colorectal cancer. Patients with high PD-L1 expression have minimal Tm cell infiltration, accompanied with a higher incidence of tumor metastasis. Single-cell sequencing revealed that PD-L1 mainly inhibited the 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. By establishing a mouse metastasis model, we found in high PD-L1 expression group, the luciferin intensity of metastatic tumor was significantly higher, the number of metastatic nodules and the weight of metastases were also increased. The number of FGFBP2(+) Tm cells in peripheral blood and in liver/lung metastases were increased. Therefore, the expression of PD-L1 in primary tumor can promote the occurrence of metastases, and FGFBP2(+)Tm cells may be involved in the formation of metastases. Furthermore, the result showed that the number of FGFBP2(+) Tm cells in metastases was positively correlated with the number of vessels in liver/lung metastases. In conclusion, we confirmed that the expression of PD-L1 in primary tumor can increase the number of FGFBP2(+) Tm cells in peripheral blood and promote tumor metastasis, which is likely to be caused by the angiogenesis of FGFBP2(+) Tm cells in metastases.