Investigation of the relationship between the CXCR4 pathway and immune response in serous papillary ovarian tumors

General Information: Serous papillary epithelial ovarian cancer (EPOC) can be divided into two groups where the immune response to the tumor is either activated or inhibited. Longer disease-free survival and overall survival have been demonstrated in patients with activated immune response (TIL positive). CXCR4 and its ligand CXCL12 (SDF-1) may be effective in cancer chemotaxis, progression, and metastasis. The presence of CXCL12 in the tumor bed increases the tumor-promoting effect of immunosuppressive CXCR4+ Tregs and plasmacytoid dendritic cells (pDC). EPOC is classified as TIL positive and negative, and the association of the CXCL1-CXCR4- CXCR7 chemokine pathway in these two groups and its effect on survival was investigated. Material and Method: The thesis was conducted retrospectively with the pathological specimens and patient files of 86 patients who had been operated in the last 10 years at the Department of Pathology and Ondokuz Mayıs University Department of Medical Biology. Pearson correlation and logistic regression analysis were used for the association of CXCL12 expression and immunohistochemical (IHC) CXCR4-CXCR7 receptor positivity in the immune and non-immune subgroups. The survival difference between the groups was compared by Kaplan-Meier and log-rank methods. P<0.05 was considered statistically significant. Results: The average progression-free survival time was 30.3 months (1-137, standard deviation: 39.6) and the average overall survival time was 56.2 months (1.9- 194 standard deviation: 39.6). Strong expression of CXCR7 in the tumor reduces the number of TILs [P<0.01 binary logistic regression, OR:0.17 (0.05-0.56) 95% CI]. Strong expression of CXCR4 in the tumor (IHC) reduces the number of CD8+ lymphocytes [P<0.05 binary logistic regression, OR:0.033 (0.02-0.66) 95% CI]. Disease-free and overall survival do not change if the fold change value of CXCL12 is above or below 0.4 (log-rank test). Conclusion: CXCL12 expression is not an independent prognostic factor in EPOC. The presence of chemokine receptors CXCR7 and CXCR4 intensively in the tumor reduces the entry of T lymphocytes into the tumor due to the scarcity of free ligand. Expression of CXCL12 above a certain threshold increases the number of TILs, and this relationship is not altered by CXCR7 or CXCR4 expression. Neoadjuvant chemotherapy increases the number of CD8+ T lymphocytes without changing the expression of CXCL12. In light of the current study, in patients with low CXCL12 expression, the blockade of CXCR7 could be considered for use with PD-1/PDL-1 antagonists to change the immune profile of the tumor