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501 LOX1 and NALP3: from immune tolerance disruption in pregnancy complications to immune escape in endometrial cancer
  1. V Bruno1,
  2. G Corrado2,
  3. L Ronchetti3,
  4. B Chiofalo1,
  5. M Iacobelli4,
  6. A Lobascio4,
  7. MA Carosi5,
  8. P Nisticò6,
  9. G Piaggio3 and
  10. E Vizza1
  1. 1IRCCS—Regina Elena National Cancer Institute, Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, Rome, Italy
  2. 2Fondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento Scienze della Salute della Donna, del Bambino, e di Sanità Pubblica, Ginecologia Oncologica, Rome, Italy
  3. 3IRCCS—Regina Elena National Cancer Institute, Department of Research, Diagnosis and Innovative Technologies, UOSD SAFU, Rome, Italy
  4. 4IRCCS—Regina Elena National Cancer Institute, Oncofertility Centre, Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, Rome, Italy
  5. 5IRCCS—Regina Elena National Cancer Institute, Anatomy Pathology Unit, Department of Research, Diagnosis and Innovative Technologies, Rome, Italy
  6. 6IRCCS-Regina Elena National Cancer Institute, Unit of Tumor Immunology and Immunotherapy, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Rome, Italy


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.

Abstract 501 Figure 1

Immunohistochemical staining on formalin-fixed paraffin-embedded samples of endometrical tissue showing expression of LOX-1 and NALP3 markers

Abstract 501 Table 1

Clinical and pathologic features of enrolled features

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.

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