CXCL11 Correlates with Anti-tumor Immune Microenvironment and Improved Prognosis in Colon Cancer

Abstract Background: CXCL11 has been considered to be responsible for tumor development, but the specific effect of CXCL11 in colon cancer was still obscure. Therefore, the prognostic value and immunological regulation effect of CXCL11 in colon cancer were evaluated in this study.Methods: Three independent datasets were used for mRNA-related analysis: one dataset from the Cancer Genome Atlas (TCGA, n=451) and two single-cell RNA sequencing (scRNA-seq) datasets from Gene Expression Omnibus (GEO): GSE146771 and GSE132465. In addition, the patient cohort (the Yijishan Hospital cohort, YJSHC, n=108) was utilized for cell infiltration-related analysis, accordingly. Both CXCL11 mRNA expression and CXCL11+ (CXCL11-producing) cells were assessed in colon cancer, whose effect on prognosis and immunological regulation was also studied. Results: High CXCL11 expression were associated with better prognosis in colon cancer, which was still significant even if clinicopathological factors were adjusted. Furthermore, CXCL11 positively correlated with anti-tumor cells infiltration, such as CD8+ T cells and natural killer cells. Meanwhile, CXCL11 correlated positively with several genes associated with DC, NK and T recruitment，and a gene set of cytotoxic genes. Notably, CXCL11 correlated positively with several immune checkpoint related genes including of PD-L1. Conclusions: CXCL11 contributed to anti-tumor immune microenvironment and could improve prognosis in patients with colon cancer. Especially, it’s a potential approach that inducible expression of CXCL11 by genetic and pharmacological interventions is able to improve prognosis and response to anti-PD-1 (programmed cell death protein-1) antibody treatment in colon cancer. However, it requires to be verified by further prospective investigations.