Liposarcomas (LPS) are the most frequent malignancies in the soft tissue sarcoma family and consist of five distinctive histological subtypes, termed well-differentiated LPS, dedifferentiated LPS (DDLPS), myxoid LPS (MLPS), pleomorphic LPS, and myxoid pleomorphic LPS. They display variations in genetic alterations, clinical behavior, and prognostic course. While accumulating evidence implicates a crucial role of the tumor immune contexture in shaping the response to anticancer treatments, the immunological landscape of LPS is highly variable across different subtypes. Thus, DDLPS is characterized by a higher abundance of infiltrating T cells, yet the opposite was reported for MLPS. Interestingly, a recent study indicated that the frequency of pre-existing T cells in soft tissue sarcomas has a predictive value for immune checkpoint inhibitor (CPI) therapy. Additionally, B cells and tertiary lymphoid structures were identified as potential biomarkers for the clinical outcome of LPS patients and response to CPI therapy. Furthermore, it was demonstrated that macrophages, predominantly of M2 polarization, are frequently associated with poor prognosis. An improved understanding of the complex LPS immune contexture enables the design and refinement of novel immunotherapeutic approaches. Here, we summarize recent studies focusing on the clinicopathological, genetic, and immunological determinants of LPS.

3rd Department of Surgery 1st Faculty of Medicine Charles University University Hospital Motol 5 Úvalu 84 150 06 Prague Czech Republic

Department of Immunology 2nd Faculty of Medicine Charles University University Hospital Motol 5 Úvalu 84 150 06 Prague Czech Republic

Department of Radiation Oncology Eberhard Karls University Tuebingen Hoppe Seyler Straße 3 72076 Tuebingen Germany

Department of Radiation Oncology Medical University of Vienna Waehringer Guertel 18 20 1090 Vienna Austria

Department of Surgery Oncology and Gastroenterology University of Padova Via Gattamelata 64 35128 Padova Italy

German Cancer Consortium Im Neuenheimer Feld 280 69120 Heidelberg Germany

Institute of Immunology Faculty of Medicine Carl Gustav Carus TU Dresden Fetscherstraße 74 01307 Dresden Germany

Institute of Pathology University Hospital Carl Gustav Carus Fetscherstraße 74 01307 Dresden Germany

National Center for Tumor Diseases University Hospital Carl Gustav Carus TU Dresden Fetscherstraße 74 01307 Dresden Germany

Veneto Institute of Oncology IOV IRCCS Via Gattamelata 64 35128 Padova Italy

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A comprehensive analysis of CD47 expression in various histological subtypes of soft tissue sarcoma: exploring novel opportunities for macrophage-directed treatments