Endometrial Cancer Immune Escape Mechanisms: Let Us Learn From the Fetal-Maternal Interface.

Valentina Bruno,Denisa Baci,Giacomo Corrado,Adriana Albini,Enrico Vizza,Livia Ronchetti,Douglas M Noonan,Benito Chiofalo,Maria Antonia Carosi,Giulia Piaggio,Emilio Piccione

doi:10.3389/fonc.2020.00156

Abstract

The immune escape mechanisms at the base of tumor progression in endometrial cancer mimic immune tolerance mechanisms occurring at the maternal–fetal interface. The biological and immunological processes behind the maternal–fetal interface are finely tuned in time and space during embryo implantation and subsequent pregnancy stages; conversely, those behind cancer progression are often aberrant. The environment composition at the maternal–fetal interface parallels the pro-tumor microenvironment identified in many cancers, pointing to the possibility for the use of the maternal–fetal interface as a model to depict immune therapeutic targets in cancer. The framework of cancer environment signatures involved in immune adaptations, precisely timed in cancer progression, could reveal a specific “immune clock” in endometrial cancer, which might guide clinicians in patient risk class assessment, diagnostic workup, management, surgical and therapeutic approach, and surveillance strategies. Here, we review studies approaching this hypothesis, focusing on what is known so far about oncofetal similarities in immunity with the idea to individualize personalized immunotherapy targets, through the downregulation of the immune escape stage or the reactivation of the pro-inflammatory processes suppressed by the tumor.

Highlights

Innate and adaptive immune response affects development and progression of cancer through a process named immunoediting [1]
A deep knowledge of the interplay between positive and negative immunological molecular players and its timing in endometrial cancer (EC) development and progression is still missing; several findings so far indicate that the immune escape mechanisms are at the base of EC progression and could be due to similar immune tolerance modulations occurring at the maternal–fetal interface [24]
We have described a proangiogenic function in natural killer (NK) cells isolated from the peripheral blood and tumorinfiltrated cells of cancer patients [54, 58,59,60] and the expression of angiogenin, CXCR4/CXCL12, MMP2, MMP9, and tissue inhibitor for matrix metalloproteinases (MMPs) (TIMP)-1 and TIMP-2 in NK cells from the peripheral blood and tumor-infiltrated cells of patients with colon cancer [59], which are molecules secreted by decidual NK (dNK) cells [55, 65,66,67]

Summary

INTRODUCTION

Innate and adaptive immune response affects development and progression of cancer through a process named immunoediting [1]. There is a parallelism between biological processes behind cancer progression and those behind the maternal–fetal interface such as proliferation, invasion, and angiogenesis [2] While these processes are finely tuned during embryo implantation stages, they are often aberrant in carcinogenesis. A deep knowledge of the interplay between positive and negative immunological molecular players and its timing in EC development and progression is still missing; several findings so far indicate that the immune escape mechanisms are at the base of EC progression and could be due to similar immune tolerance modulations occurring at the maternal–fetal interface [24]. The immune escape pathways underlying the progression from physiological endometrium to carcinoma could represent new targets for personalized immunotherapy by the reactivation of the pro-inflammatory response processes suppressed by the tumor.

Tumor invades cervical stroma but does not extend beyond the uterus

CONCLUSIONS