Identification of CXCL13 as a Promising Biomarker for Immune Checkpoint Blockade Therapy and PARP Inhibitor Therapy in Ovarian Cancer

Abstract

Ovarian cancer has poor response rates to immune checkpoint blockade (ICB) therapy, despite the use of genomic sequencing to identify molecular targets. Homologous recombination deficiency (HRD) is a conventional indicator of genomic instability (GI) and has been used as a marker for targeted therapies. Indicators reflecting HRD status have shown potential in predicting the efficacy of ICB treatment. Public databases, including TCGA, ICGC, and GEO, were used to obtain data. HRD scores, neoantigen load, and TMB were obtained from the TCGA cohort. Candidate biomarkers were validated in multiple databases, such as the Imvigor210 immunotherapy cohort and the open-source single-cell sequencing database. Immunohistochemistry was performed to further validate the results in independent cohorts. CXCL10, CXCL11, and CXCL13 were found to be significantly upregulated in HRD tumors and exhibited prognostic value. A comprehensive analysis of the tumor immune microenvironment (TIME) revealed that CXCL13 expression positively correlated with neoantigen load and immune cell infiltration. In addition, single-cell sequencing data and clinical trial results supported the utility of CXCL13 as a biomarker for ICB therapy. Not only does CXCL13 serve as a biomarker reflecting HRD status, but it also introduces a potentially novel perspective on prognostic biomarkers for ICB in ovarian cancer.

Keywords: CXCL13; Homologous recombination deficiency; Immune checkpoint blockade; Ovarian cancer.