大肠癌微环境中趋化因子表达分泌决定免疫细胞功能的动态平衡，影响肿瘤进展。我们发现CXCL5在大肠癌中高表达，在体内通过诱导中性粒细胞聚集促进肿瘤进展。最新观点将肿瘤相关中性粒分为促肿瘤的低密度中性粒（LDN）和抑肿瘤的高密度中性粒（HDN）。前期证实早期大肠癌以HDN为主，进展期大肠癌LDN比例升高，并与CXCL5表达呈正相关；LDN上清液中Arginase-1/CCL17表达升高。因此我们提出大肠癌高表达CXCL5可能诱导HDN向LDN转化，LDN通过分泌Arginase-1/CCL17促进大肠癌进展。本项目旨在1)进一步证实LDN在进展期大肠癌中比例升高并促进肿瘤进展；2)研究CXCL5是否诱导HDN向LDN转化及分子机制；3)探讨LDN通过分泌Arginase-1/CCL17调控T细胞功能促进肿瘤进展的免疫机制。本研究有助于发现大肠癌免疫治疗新靶点，对改善大肠癌患者预后具有重要意义。

The chemokines in colorectal cancer microenvironment determine the homeostasis of immune cell function and affect tumor progression. We found that CXCL5 was highly expressed in colorectal cancer and was able to promote tumor progression in vivo via inducing neutrophil accumulation. Recent studies divide tumor-associated neutrophils into two types: protumoral low density neutrophils (LDNs) and anti-tumoral high density neutrophils (HDNs). Preliminary experiments demonstrated that HDN was mainly expressed in early colorectal cancer and the proportion of LDN in advanced colorectal cancer was increased which was positively correlated with the expression of CXCL5. The expression of Arginase-1/CCL17 in LDN supernatant was also increased. Therefore, we propose that high expression of CXCL5 in colorectal cancer may induce the conversion of HDN to LDN, and LDN may promote the progression of colorectal cancer by secreting Arginase-1/CCL17. In this project, we are planning to 1) further confirm that the proportion of LDN is increased in advanced colorectal cancer and is able to promote tumor progression; 2) study whether CXCL5 can induce HDN to convert to LDN and its molecular mechanisms; 3) explore the immune mechanisms of LDN secreting Arginase-1/ CCL17 to regulate T cell functions to build immune tolerant microenvironment then promoting tumor progression. Our study will help find new targets for immunotherapy of colorectal cancer and improve the prognosis of patients with colorectal cancer.