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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  CD 4 + ,  CD 8 + , FoxP3 + ,  CD 20 + , or programmed cell death‐1 ( PD ‐1) +  tumor infiltrating lymphocytes ( TIL s) 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 ,  TIL s were distributed in 3 patterns and T cells were more prevalent than B cells. Generally, the proportion of  TIL s 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  TIL s 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.

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