Immune characteristics of dedifferentiated retroperitoneal liposarcomas and the reliability of regional samples in evaluating their tumor immune microenvironments.

Background: Tumor immunotherapy is a new treatment breakthrough for retroperitoneal liposarcoma (RPLS), which is highly invasive and has few effective treatment options other than tumor resection. However, the heterogeneity of the tumor immune microenvironment (TIME) leads to missed clinical diagnosis and inappropriate treatment. Therefore, it is crucial to evaluate whether the TIME of a certain part of the tumor reliably represents the whole tumor, particularly for very large tumors, such as RPLS.

Methods: We conducted a prospective study to evaluate the TIME in different regions of dedifferentiated RPLS (DDRPLS) by detecting the expressions of markers such as CD4, CD8, Foxp3, CD20, CD68, LAMP3, PD-1 tumor-infiltrating lymphocytes (TILs), and PD-L1 in tumors and corresponding paratumor tissues via immunohistochemistry and RNA sequencing.

Results: In DDRPLS, very few TILs were observed. Differentially expressed genes were significantly enriched in cell part and cell functions, as well as the metabolic pathway and PI3K-Akt signaling pathway. In addition, for most tumors (70-80%), the TIME was similar in different tumor regions.

Conclusions: For most tumors (70-80%), the TIME in any region of the tumor reliably represents the whole tumor. DDRPLS may regulate cell functions by modulating the metabolic and PI3K-Akt signaling pathways to promote its malignant behavior.