CXCL10 and CCL5 as feasible biomarkers for immunotherapy of homologous recombination deficient ovarian cancer.

This study aims to identify biomarkers of ovarian cancer, specifically those tumors exhibiting homologous recombination deficiency (HRD), to contribute to the optimization of immunotherapy. We screened the differentially expressed genes coding for CXCL10 and CCL5 by analyzing the transcriptome data of patient with different HRD scores in the ovarian cancer cohort of the TCGA database and validated our results using pathological tissue sections. The cellular origin of CXCL10 and CCL5 were identified using the single-cell sequencing data extracted from the GEO database combined with the tumor mutational burden (TMB) and single nucleotide polymorphism (SNP) data obtained from the TCGA database. We found that CXCL10 and CCL5 expression levels were correlated with HRD score. Analysis of single-cell sequencing results and tumor mutation data suggested that both CXCL10 and CCL5 present in the tumor microenvironment were primarily derived from immune cells. In addition, we found that samples with high expression of CXCL10 and CCL5 also had higher stromal cell and immune cell scores, indicating low tumor homogeny. Further analysis showed that CXCL10 and CCL5 expression was associated with immune checkpoint-related genes, and the efficacy of using these proteins as biomarkers was significantly higher than that of PD-1 in predicting the effect of anti-PD-1 immunotherapy. The expression of CXCL10 and CCL5 had statistically different effects on the survival of patients, based on multivariate Cox regression. In summary, the results demonstrate that in ovarian cancer, the expression of CXCL10 and CCL5 are correlated with HRD. When CXCL10 and CCL5 are secreted by immune cells, immune cell infiltration can be chemotactic and predict the effect of immunotherapy more efficiently than using PD-1 as a biomarker. Therefore, CXCL10 and CCL5 look to be promising novel biomarkers to guide immunotherapy in ovarian cancer.