Abstract 1501: Clinical significance of tumor immune microenvironment in soft tissue sarcoma
Authors: Naoki Oike, Hiroyuki Kawashima, Akira Ogose, Hiroshi Hatano, Takashi Ariizumi, Taro Sasaki, Tetsuro Yamagishi, Hajime Umezu, Naoto Endo
Journal: Cancer Research (2019)

Abstract Background: The prognosis of patients with metastatic soft tissue sarcoma (STS) remain poor. Although immunotherapies have been attempted in patients with STS, the prognostic significance of the immune status within the tumor microenvironment in STS is not well understood. The purpose of this study is to investigate the tumor immune microenvironment and evaluate its prognostic impact for patients with STS. Material and Methods: We retrospectively evaluated the tumor immune microenvironment in 116 primary untreated STS patients with five subtypes: synovial sarcoma (SS: n=36), myxoid liposarcoma (MLS: n=32), undifferentiated pleomorphic sarcoma (UPS: n=27), leiomyosarcoma (LMS: n=11), and dedifferentiated liposarcoma (DDLS: n=10). The infiltration of CD8+ and FOXP3+ lymphocytes, CD163+ macrophages, and the expression of HLA class I and PD-L1 in the tumor were evaluated by immunohistochemistry. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Results: UPS had a higher infiltration of CD8+ and FOXP3+ lymphocytes than SS and MLS. Infiltration of CD163 + macrophages were higher in UPS, LMS, and DDLS than in SS and MLS. HLA class I expression was detected in all of UPS, LMS, and DDLS. However, HLA class I was negative in 17% of SS and 69% of MLS. Although no PD-L1 expression was observed in SS and MLS, PD-L1 expression was detected in 36% of UPS, 28% of LMS, and 25% of DDLS. Moreover, PD-L1 expression was associated with poor outcome in these subtypes. Increasing number of CD8+ lymphocytes was associated with a better OS in patients with SS. A higher infiltration of FOXP3+ lymphocytes was associated with an unfavorable OS in patients with MLS but favorable outcome in SS. Moreover, a higher infiltration of CD163+ macrophages showed a significantly worse OS and PFS in patients with SS and MLS. Conclusion: Lymphocytes and macrophages were variably infiltrated across STS subtype. UPS, LMS and DDLS, which have numerous genetic mutations, demonstrated high infiltration of lymphocytes, HLA class I and PD-L1 expression. These suggest that T-cell based immunotherapy such as immune checkpoint inhibitors may be effective in these tumor subtypes. Although the SS and MLS are less mutated and do express cancer-testis antigen NY-ESO-1 in common, expression level of HLA class I is significantly different between SS and MLS. In addition, infiltration of FOXP3+ lymphocytes have opposite effect in these tumors. These suggests different immunotherapeutic strategy might be required in these subtypes. Our results might be useful in the clinical strategy of immunotherapy in STS. Citation Format: Naoki Oike, Hiroyuki Kawashima, Akira Ogose, Hiroshi Hatano, Takashi Ariizumi, Taro Sasaki, Tetsuro Yamagishi, Hajime Umezu, Naoto Endo. Clinical significance of tumor immune microenvironment in soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1501.