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Abstract
Introduction/Background Serous papillary epithelial ovarian cancer (EPOC) exhibits differential immune responses, categorized into activated and inhibited immune responses. Patients with an activated immune response, evidenced by tumor-infiltrating lymphocytes (TIL positive), show improved disease-free and overall survival. The CXCR4/CXCL12 (SDF-1) axis is implicated in cancer chemotaxis, progression, and metastasis. In the tumor microenvironment, CXCL12 enhances the tumor-supportive roles of immunosuppressive CXCR4+ Tregs and plasmacytoid dendritic cells (pDCs). This study investigates the role of the CXCL12-CXCR4-CXCR7 chemokine pathway in EPOC, specifically in TIL positive and negative classifications, and its impact on survival.
Methodology This retrospective study analyzed pathological specimens and patient records of 86 individuals treated over the past decade at the Department of Pathology and Department of Medical Biology, Ondokuz Mayıs University. We employed Pearson correlation and logistic regression to assess the association between CXCL12 expression (mRNA) and CXCR4-CXCR7 receptor positivity (immunhistochemistry) in immune-responsive and non-responsive EPOC subgroups. Survival differences were evaluated using Kaplan-Meier and log-rank methods, and P<0.05 is considered significant.
Results The mean progression-free survival was 30.3 months (standard deviation: 39.6m), and the mean overall survival was 56.2 months (standard deviation: 39.6m). High tumor expression of CXCR7 significantly reduced TIL numbers [P<0.01, OR: 0.17 (95% CI: 0.05–0.56)]. Similarly, elevated CXCR4 expression was inversely related to CD8+ lymphocyte count [P<0.05, OR: 0.033 (95% CI: 0.02–0.66)]. No significant survival differences were observed based on CXCL12 expression levels (log-rank test).
Conclusion CXCL12 expression alone does not independently predict prognosis in EPOC. High tumor concentrations of CXCR7 and CXCR4 receptors limit T-lymphocyte infiltration due to ligand scarcity. Elevated CXCL12 expression correlates with increased TIL presence, a relationship not influenced by CXCR7 or CXCR4 levels. Neoadjuvant chemotherapy augments CD8+ T-lymphocyte counts independently of CXCL12 expression. Our findings suggest that in EPOC cases with low CXCL12 expression, CXCR7 blockade might be helpful for immune recognition of the tumor.
Disclosures None.
