The Immune Contexture of Liposarcoma and Its Clinical Implications

Abstract

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.

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

“…In our patient cohort consisting of various STS, half of the samples had more than 2/3 of the total tumor area positive on CD47 staining. To offer a more profound insight, we have divided LPS according to their histological subtypes, because we are aware of their considerable differences (Resag et al 2022 ). Interestingly, only one WDLPS out of all 22 LPS specimens, did not express CD47.…”

Prognostic impact of the post-treatment T cell composition and spatial organization in soft tissue sarcoma patients treated with neoadjuvant hyperthermic radio(chemo)therapy

“…Also RHT, a frequently used treatment for extremity STS, was reported to show immunogenic effects ( 37 ). Boosting the pre-existing immune TME is of particular interest for STS, as they generally exhibit a low to moderate T cell infiltration compared to other tumor entities with major differences between STS subtypes ( 38 – 42 ). However, in our study, CD3 + and CD8 + T cell densities showed a trend to decrease following neoadjuvant therapy.…”

Oncostatin M and Nivolumab Affect the Cytotoxic T-Cell Proportions and the Susceptibility to TRAIL-Induced Death in Non-Leukocyte Cell Subpopulations in Soft Tissue Sarcomas

“…For instance, five distinct subtypes of liposarcoma display major variations in the composition of the TME [29]. While dedifferentiated liposarcoma became the predominant liposarcoma subtype evaluated in clinical trials with immune checkpoint inhibitors due to its relatively high infiltration with T cells, myxoid liposarcoma has become a prime target for CAR T-cell therapy [41]. Since a large portion of dedifferentiated liposarcomas derive from well-differentiated liposarcomas, we aimed to evaluate the immunotherapy responses in this particular liposarcoma subtype [41].…”

“…While dedifferentiated liposarcoma became the predominant liposarcoma subtype evaluated in clinical trials with immune checkpoint inhibitors due to its relatively high infiltration with T cells, myxoid liposarcoma has become a prime target for CAR T-cell therapy [41]. Since a large portion of dedifferentiated liposarcomas derive from well-differentiated liposarcomas, we aimed to evaluate the immunotherapy responses in this particular liposarcoma subtype [41]. However, our limited cohort size hampered prediction of treatment response based on histological subtype of STS.…”