Human leukocyte antigen I is significantly downregulated in patients with myxoid liposarcomas

Abstract

The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.

The Immune Contexture of Liposarcoma and Its Clinical Implications

“…Among the LPS subtypes, several reports demonstrated that DDLPS harbors the highest TIL numbers, followed by WDLPS and MLPS [ 86 , 87 , 88 , 89 ]. Since PLPS is a rare LPS subtype, data is scarce and inconsistent.…”

“…Yan et al observed in PLPS the lowest TIL rate of all subtypes in a cohort of retroperitoneal LPS [ 88 ]. In contrast, Oike et al reported that PLPS have CD8 + T cell levels between that of DDLPS and MLPS but exhibit the highest CD4 + and FoxP3 + levels of all LPS subtypes [ 89 ].…”

“…Several studies demonstrated that CD8 + T cells represent the majority of T cells in LPS, followed by CD4 + T cells and FoxP3 + Tregs [ 88 , 89 , 98 ]. However, results regarding the prognostic significance of LPS-infiltrating T cells are less consistent.…”

“…In the karyotypically complex DDLPS, high numbers of CD4 + T cells correlated significantly with a favorable three-year recurrence-free survival (RFS) [ 98 ], while another study found no association between CD4 + , CD8 + , and FoxP3 + infiltration and disease progression [ 89 ]. However, a link between FoxP3 + Treg infiltration and a prolonged OS was also reported [ 86 ].…”

Sarcoma Common MHC-I Haplotype Restricts Tumor-Specific CD8+ T Cell Response

“…In turn, CD8+ T cells require CD4+ T helper cells activated via HLA class II molecules (categorized into HLA-DR, -DQ, and -DP loci) [ 22 , 23 ]. Selective loss or genomic alteration of HLA class I haplotypes, together with the co-option of immune checkpoint PD-1/PD-L1, have been described in cancer as an escape mechanism to host immune defenses [ 24 , 25 , 26 , 27 ]. Evidence suggests that reduced HLA class I expression is associated with high PD-L1 positive immunostaining [ 28 , 29 , 30 , 31 ].…”