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CXCL13 shapes tumor immune microenvironment in ovarian cancer with homologous recombination deficiency

Year: 2023

Type: article

Abstract: CXCL13 shapes tumor immune microenvironment in ovarian cancer with homologous recombination deficiencyRecently, immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase inhibitors (PARPi) have played a pivotal role in prolonging the recurrence-free survival of patients with ovarian cancer (OC).1,2 Although PARPi have revolutionized the treatment of OC, the absence of reliable predictive biomarkers limits the broad application of ICIs for patients with homologous recombination (HR) deficiency (HRD).3 CXC-chemokine ligand 13 (CXCL13) is a cytokine constitutively secreted in the stromal cells of the B-cell region of secondary lymphoid tissue.4 It exclusively binds to the chemokine receptor CXCR5, which is abundantly expressed in subsets of mature circulating B lymphocytes, follicular helper T cells, and skin-derived dendritic cells, and governs the migration of these cells into secondary lymphoid organs in response to the CXCL13 gradient.5 In this study, we aimed to elucidate the role of CXCL13 in shaping the tumor immune microenvironment (TIME) in HR-deficient OC and to explore its relationship with the cGAS-STING signaling pathway.Due to the absence of matched para-cancerous tissues in The Cancer Genome Atlas (TCGA) cohort, we utilized the GTEx database of normal ovarian samples to analyze CXCL13 expression.The expression of CXCL13 was significantly higher in cancer compared with normal tissues (Fig. 1A).In addition, we obtained a similar conclusion at the protein expression level (Fig. S1A).The effect of CXCL13 on the prognosis reveals that patients with high CXCL13 expression had superior overall survival (Fig. 1B; Log-rank P Z 0.002), and high CXCL13 expression was an independent prognostic factor (Fig. S1B).The analysis using the Gene Expression Omnibus dataset yielded similar results (Fig. S1C).Moreover, we confirmed that HRD status was closely related to CXCL13 in 20 FFPE samples (HRD-H: 15; HRD-L: 5) (Fig. S2A).The clinical characteristics of all Peer review under responsibility of Chongqing Medical University.

Source: Genes & Diseases

DOI: 10.1016/j.gendis.2023.101200