肠癌组织PD-L1的表达抑制CD45RO+T细胞组织浸润及其机制研究

循环免疫细胞的组织浸润程度及细胞功能决定着肿瘤的发生、发展。课题组通过对比65例结肠癌患者血液与肿瘤内免疫细胞的含量，发现PD-L1高表达患者外周血CD45RO+T细胞含量增高，而组织中CD45RO+T细胞含量反而下降，提出“肿瘤细胞PD-L1的表达抑制CD45RO+T细胞的组织浸润”这一假设。我们发现肿瘤细胞PD-L1蛋白能够减少肿瘤细胞自身分泌的CCL19等趋化因子，也能够抑制DC细胞分泌CXCL9、CXCL10趋化蛋白，并且很可能以此减弱CD45RO+T细胞的迁移能力来抑制其组织浸润；除此之外，PD-L1蛋白能够抑制血液及组织中CD45RO+T细胞向效应型CD45RO+T细胞的转化；运用单细胞测序技术，进一步分析已浸润的CD45RO+T细胞的TCR多样性对细胞功能的影响。本研究从趋化因子的分泌、受体的表达、细胞分化等层面探究PD-L1对CD45RO+T细胞组织浸润和细胞功能的影响。

The infiltration degree and cell function of circulating immune cells determine the occurrence and development of tumors. By comparing the content of immune cells in the blood and tumor of 65 CRC patients, we found that patients with high PD-L1 expression have a increased number of CD45RO+ T cells in peripheral blood, while the content of CD45RO+ T cells in tumor are decreased. We proposed "The expression of PD-L1 inhibits the tissue infiltration of CD45RO+ T cells ". We found that tumor PD-L1 protein can reduce CCL19 and other chemokines secreted by tumor cells itself, and can also inhibit DC cells from secreting chemokines CXCL9 and CXCL10, and it is likely to reduce the migration ability of CD45RO+ T cells to inhibit its tumor infiltration; in addition, PD-L1 protein can inhibit the transformation of CD45RO+ T cells into effector CD45RO+ T cells in blood and tumors; Using single-cell sequencing technology to further analyze the effects of TCR diversity of infiltrated CD45RO+ T cells on cell function. This study explored the effects of PD-L1 on CD45RO+ T cell tumor infiltration and cell function from the aspects of chemokine secretion, receptor expression, and cell differentiation.