Lox1 and nalp3: from immune tolerance disruption in pregnancy complications to immune escape in endometrial cancer

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 Conclusion* An increased LOX-1 and a decreased NALP3 expression seems be associated with EC progression. To identify patients at risk of developing EC from pre-cancerous lesions, by searching potential immune prognostic factors, such as LOX-1 and NALP3 on endometrial biopsy, could re-defy the actual EC risk classes through a potential ’immune score’ creation. Nevertheless, further studies are needed to define EC transcriptome immune-based signature. Furthermore, pathways detected by deciphering the immune changes linked to EC progression, could be potential target for immunotherapy.