Integration of morphological and molecular characteristics of the synovial sarcoma microenvironment into a personalized treatment concept: a review

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Abstract

This review summarizes data on the morphological and molecular characteristics of the tumor microenvironment (TME) of synovial sarcoma and shows how the integration of these parameters can be used for choosing personalized treatment.

Publications from 2015–2025 (with priority given to 2023–2025) were analyzed across key areas: tumor immune landscape; stromal and vascular components; spatial organization of the TME; epigenetic regulation and therapeutic strategies, including Tcell receptorbased approaches; as well as data from multiplex immunomorphology, singlecell and spatial transcriptomic profiling, and clinical studies of immunotherapy.

The TME of synovial sarcoma was found to be highly heterogeneous and often immunologically “cold,” with limited effector T cell infiltration and a predominance of immunosuppressive myeloid populations (macrophages / myeloid-derived suppressor cells); however, a subset of cases shows signs of T cell inflammation that may predict response to treatment. Modern spatial approaches and single-cell RNA sequencing refine the compartmentalization of the TME and identify cellular states of tumor cells and stroma associated with invasion and resistance. Key personalization directions include: (1) stratification by antigen expression (NY-ESO-1, MAGE-A4, PRAME) and antigen presentation status; (2) combining T cell receptor-based therapy with TME modulators (epigenetic drugs, signaling pathway inhibitors, anti-angiogenic/anti-fibrotic strategies); and (3) digital TME morphometry using whole-slide images (WSI) as a reproducible source of biomarkers. Thus, the integration of morphological, immune, and molecular characteristics of the TME forms the basis for practice-oriented stratification of patients with synovial sarcoma and rational selection of personalized therapeutic combinations.

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About the authors

Dmitriy V. Bulanov

Priorov Central institute for Trauma and Orthopedics; The Russian National Research Medical University named after N.I. Pirogov

Author for correspondence.
Email: dbulanov81@gmail.com
ORCID iD: 0009-0005-3772-6643
SPIN-code: 2641-6658

MD, Cand. Sci. (Medicine), Associate Professor

Russian Federation, Moscow; Moscow

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