Association of CXCR7 and CXCR4 expression with tumor immune phenotypes in tubo-ovarian high-grade serous carcinoma

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are associated with favorable outcomes in high-grade serous ovarian carcinoma (HGSC); however, the tumor microenvironment may modulate immune cell infiltration. This study aimed to evaluate the association between tumor and stromal expression of CXCL12, tumor expression of CXCR4 and CXCR7, immune phenotypes, and survival outcomes in tubo-ovarian HGSC. METHODS: Eighty-six patients with primary tubo-ovarian HGSC who underwent cytoreductive surgery were retrospectively analyzed. Immunohistochemical expression of CXCL12 (tumor and stroma), CXCR4, and CXCR7 was assessed. TILs were semi-quantitatively scored and dichotomized as low (score 1) or high (scores 2-3). Immune phenotypes were classified as immunogenic, immune-excluded, or immune-ignorant. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier methods, log-rank tests, and Cox regression. Multivariable logistic regression was used to identify factors associated with high TILs. RESULTS: Median RFS was 23.2 months (95% CI, 19.2-27.1) and median OS was 47.3 months (95% CI, 36.3-55.0). RFS differed significantly across immune phenotypes (log-rank p=0.047), with shorter RFS observed in the immune-excluded phenotype compared with the immunogenic phenotype (hazard ratio, 2.20; 95% CI, 1.14-4.25). High tumor CXCR7 expression was independently associated with a lower likelihood of high TILs (adjusted odds ratio, 0.22; 95% CI, 0.07-0.65). CXCL12 expression was not associated with survival outcomes. CONCLUSION: Tumor CXCR7 expression is associated with reduced lymphocytic infiltration and an immune-excluded phenotype in HGSC, suggesting a potential role of the CXCR7 axis in shaping the tumor immune microenvironment.