LOX1 AND NALP3: FROM IMMUNE TOLERANCE DISRUPTION IN PREGNANCY COMPLICATIONS TO IMMUNE ESCAPE IN ENDOMETRIAL CANCER

Abstract Introduction/Background*Endometrial cancer (EC) patients have a good prognosis at early stages, but for recurrent or metastatic EC the prognosis remains poor. EC treatments are related to known prognostic factors included in ESMO-ESGO-ESTRO risk classes classification, but they are not sufficient to predict outcomes or recurrence rate of early stages. To improve patient clinical management and allow personalized therapy a better characterization of risk classes in EC is needed. To fill this gap, we investigated EC immune escape processes, customized on the knowledge of maternal-fetal interface immune mechanisms, since the two processes share common pathways. Methodology This has been addressed by the identification of potential shared immune-based signatures between maternal-fetal interface and EC, such as those linked to lectin-type oxidized LDL receptor 1 (LOX-1) and NALP3 inflammasome, in order to achieve a potential immune score implementation to better characterize EC risk classes. The immunohistochemical assessment of LOX-1 and NALP3 was performed on formalin-fixed paraffin-embedded (FFPE) endometrial tissues. Result(s)*41 patients divided in 3 groups were enrolled: healthy endometrial tissue, endometrial hyperplasia and EC. We detected an increased expression of LOX-1, by immunohistochemistry (IHC), within the endometrial carcinoma tissues, a lower expression in cases of hyperplasia, to arrive to an absent staining in the healthy endometrial tissue (*p< 0.05, *Kruskal-Wallis followed by Mann-Whitney test). This grading is inverted in NALP3, which expression appears to be lower in EC (*p< 0.05). A proportional relationship between LOX-1 and NALP3 expression was demonstrated (p=0.006, Spearman test, confirmed through a linear regression test): increasing the expression of LOX-1, NALP3 decreases.