Immunotherapy for High-Grade Endometrial Stromal Sarcoma: A Narrative Review Bridging Molecular Insights to Clinical Translation

Liubiqi Zhao¹Yunyi Su¹Xiaoling Li²Wang Fang¹Li He¹Limei Fan³Lushuang Zhang^1*

• ¹Chengdu Women and Children’s Central Hospital, Chengdu, China
• ²Chongqing Medical University, Chongqing, China
• ³Jilin University, Changchun, China

High-grade endometrial stromal sarcoma (HGESS) is a rare solid malignancy characterized by a poor prognosis and highly aggressive behavior. Currently, surgical resection remains the primary treatment for HGESS. Radiotherapy and chemotherapy can address local symptoms and enhance the quality of life of patients; however, they do not improve patient survival rates. Recent studies have found that the molecular characteristics of HGESS (such as gene fusions like YWHAE-NUTM2, ZC3H7B-BCOR, etc.) drive the high invasiveness of the tumor. Although immunotherapy has achieved significant breakthroughs in solid tumors, the immunosuppressive microenvironment of HGESS remains a key focus for future immunotherapy research. This narrative review comprehensively analyzes the interactions between alterations in the tumor microenvironment and immune escape mechanisms in HGESS. It also proposes a diverse range of immunotherapy options, including Oncolytic virus therapy, adoptive cell transfer therapy, immune checkpoint inhibitors, cancer vaccines, and combination strategies. We hold the view that a profound comprehension of the molecular immunological characteristics of HGESS, the identification of effective biomarkers, and the implementation of well-designed clinical studies are the indispensable routes to successfully translate immunotherapy into an effective treatment for this intractable HGESS.