Comprehensive immune characterization and T‐cell receptor repertoire heterogeneity of retroperitoneal liposarcoma

Abstract

Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas and lacks effective treatment. This study aimed to provide a thorough profile of immune characteristics of RLPS. This study included 56 RLPS patients. Multisite tumor tissues were collected from 16 patients. Immunohistochemistry was carried out to identify CD4+, CD8+, FoxP3+, CD20+, or programmed cell death‐1 (PD‐1)+ tumor infiltrating lymphocytes (TILs) and Programmed cell death ligand‐1 (PD‐L1) expression in tumor tissues. Ultradeep sequencing of T‐cell receptor (TCR) β‐chain gene was carried out in 42 tumor samples as well as peripheral blood samples collected from 6 patients. In RLPS, TILs were distributed in 3 patterns and T cells were more prevalent than B cells. Generally, the proportion of TILs decreased and PD‐L1 expression increased with tumor progression. Patients with higher PD‐1/PD‐L1 expression tended to have poorer prognosis, whereas patients with tertiary lymphoid structure tended to have a favorable disease‐free survival. Although T‐cell clones in tumors were quite different from those in peripheral blood, TCR sequencing showed low TCR repertoire reads as well as polyclonal status within tumors, which indicated limited T cell response in the tumors. Both TILs distribution and TCR repertoires suggested spatial immune heterogeneity in RLPS. Our research described the immune landscape of RLPS, and suggested RLPS might be a kind of tumor with low T cell infiltration as well as great immune heterogeneity. Therefore, strategies that can facilitate lymphocytic infiltration and immune reactivity need to be developed in the future to improve the efficacy of immunotherapy.

Recent Advancement in Atypical Lipomatous Tumor Research

“…A study showed liposarcoma patients exhibit high expression (92-100%) of PDL1 in well-differentiated liposarcoma tumor cells [83,84], and multivariate analysis revealed a PDL1-highly expressed sarcoma was closely associated with shorter survival [85]. In the dedifferentiated liposarcoma, high PDL1 expression was associated with statistically significant unfavorable recurrence-free survival and overall survival rates [86,87].…”

Immunotherapy for sarcomas: new frontiers and unveiled opportunities

“… 11 Other groups have also shown that UPS, leiomyosarcoma and LPS patients have increased expression of PD-1/PD-L1, suggesting that these sarcoma subtypes could potentially respond to ICB treatment. 10 14 …”

Sarcomas: Immune biomarker expression and checkpoint inhibitor trials

“…Studies characterizing T cell infiltrates in bone sarcomas have been published [29][30][31], with more recent studies focussing on soft-tissue sarcomas. A majority of studies find CD8+ T cells to be more abundant [11,[32][33][34] relative to FOXP3+ T regulatory cells [32][33][34][35][36]. When divided based on karyotype complexity, copy number-driven sarcomas (DDLPS [11], leiomyosarcoma [35,37], UPS, and myxofibrosarcoma [38]) had higher T cell infiltration than translocation-associated subtypes [11].…”