Prognostic impact of the tumor immune microenvironment in synovial sarcoma

• Published in: Cancer science Vol. 109; no. 10; pp. 3043 - 3054
• Main Authors: Oike, Naoki, Kawashima, Hiroyuki, Ogose, Akira, Hotta, Tetsuo, Hatano, Hiroshi, Ariizumi, Takashi, Sasaki, Taro, Yamagishi, Tetsuro, Umezu, Hajime, Endo, Naoto
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2018; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Aged; Antigens; Apoptosis; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Biomarkers, Tumor - immunology; Biopsy; Bone surgery; Cancer therapies; CD163 antigen; CD163+ macrophage; CD4 antigen; CD8 antigen; Cell Line, Tumor; Chemotherapy; Child; Disease-Free Survival; Female; Foxp3 protein; Gene expression; Histocompatibility antigen HLA; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Hospitals; Humans; Immune status; Immunoglobulins; Immunohistochemistry; Immunotherapy; Kaplan-Meier Estimate; Ligands; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Macrophages; Macrophages - immunology; Male; Medical prognosis; Metastases; Metastasis; Middle Aged; Neoplasm Staging; Original; Patients; PD-L1 protein; Prognosis; programmed death ligand 1; Retrospective Studies; Sarcoma, Synovial - immunology; Sarcoma, Synovial - mortality; Sarcoma, Synovial - pathology; Sarcoma, Synovial - surgery; Studies; Synovial sarcoma; tumor immune microenvironment; Tumor Microenvironment - immunology; Tumors; Young Adult; Japan; synovial sarcoma; programmed death ligand 1; CD163+ macrophage; tumor immune microenvironment; prognosis
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13769

The association between the immune status within the tumor microenvironment and prognosis in synovial sarcoma is not well understood. We aimed to investigate the tumor immune microenvironment and analyze its prognostic impact for patients with synovial sarcoma. A total of 36 primary patients who were treated in our institution were retrospectively evaluated. Infiltration of lymphocytes (CD4+, CD8+, and FOXP3+), CD163+ macrophages, and expression of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD‐L1) were evaluated by immunohistochemistry. Moreover, we investigated PD‐L1 and programmed death ligand 2 (PD‐L2) mRNA expression in 19 of the 36 cases, using real‐time PCR. The Kaplan‐Meier method was used to estimate overall survival and progression‐free survival. Infiltration of lymphocytes and macrophages varied among the patients. Furthermore, the expression of HLA class I was negative or downregulated in 11 specimens. No PD‐L1 expression was observed using immunohistochemistry. Moreover, although PD‐L1 mRNA expression was observed in 18 of 19 specimens, the expression level was low. A higher infiltration of CD8+ or FOXP3+ lymphocytes in patients was associated with a favorable overall survival. In addition, a higher infiltration of CD163+ macrophages indicated a significantly worse overall and progression‐free survival. Infiltration of CD4+ lymphocytes, HLA class I, PD‐L1, and PD‐L2 expression were not associated with patient prognosis. This represents the first report investigating the tumor immune microenvironment as a prognostic factor in synovial sarcoma, indicating that CD163+ macrophages are associated with tumor progression. Our results underscore the clinical significance of the tumor immune microenvironment in synovial sarcoma. We are the first to investigate the tumor immune environment of primary non‐treated patients with synovial sarcoma and analyze its clinical significance in synovial sarcoma. We showed that the infiltration of CD163+ macrophages plays an important role in disease progression in patients with synovial sarcoma.