Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas

Abstract

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy in recent years. The aim of this study is to evaluate the PD-1/PD-L1 expressions in sarcomas and to determine association between PD-1/PD-L1 expressions and clinical/pathological properties in some sarcoma subtypes. Formalin-fixed, paraffin-embedded tissue samples from 65 cases with sarcomas were analyzed. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions in tumor tissue and microenvironment, separately. PD-1 expression in tumor tissue and microenvironment was detected in 11 (17 %) and 8 (12 %) cases, respectively. PD-L1 expression in tumor tissue and microenvironment was detected in 19 (29 %) and 20 cases (30 %), respectively. None of the 5 Ewing sarcomas involving bone showed PD-1/PD-L1 expression, while 2 of 3 cases with Ewing sarcomas involving soft tissue showed PD-1 and PD-L1 expression. Among 5 cases with Kaposi sarcoma, four showed PD-1 and/or PD-L1 expression in tumor or microenvironment. PD-1/PD-L1 expressions were detected 3 of 6 cases with pleomorphic sarcoma, 2 of 4 cases with peripheral nerve sheath tumors and 1 of 4 cases with synovial sarcoma. Interestingly, strongest PD-1/PD-L1 expressions in our study group were detected in 2 sarcoma cases with the history of giant cell tumor. PD-1 and PD-L1 expressions are up to 30 % of the cases with sarcomas. It may be rational to target programmed death pathway in Kaposi sarcoma, pleomorphic sarcoma and peripheral nerve sheath tumors. Strong expression of PD-1/PD-L1 in cases with previous giant cell bone tumor has been found to be interesting and must be studied in giant cell tumor samples.

Programmed death ligand 1 (pd-l1) expression in malignant mesenchymal tumors

“…Inflammatory cells are present in almost all of the sarcomas, and 30% of lymphocytes and 58% of macrophages expressed PD-L1 (12). Paydas et al also recorded that 30% of cells forming tumor microenvironment expressed PD-L1 (14). Our result of 14.4% PD-L1 positive tumor-infiltrating inflammatory cells seems to be lower than expected, possibly due to the use of tissue microarrays instead of whole sections.…”

“…In line with this, in a study including 53 MPnSTs, 13% were shown to express PD-L1 in tumor cells (15), while in others 25% and 21% of MPnSTs were PD-L1 positive (11,14). Some studies also confirmed a significant correlation between PD-L1 expression and advanced clinicopathological parameters, such as higher clinical stage, presence of distant metastasis, as well as higher histological grade, poor differentiation of tumor, and tumor necrosis (8,9).…”

“…We found a very low level (4%) of co-expression of PD-L1 in both tumor and tumor infiltrating inflammatory cells. In the series of Paydas et al, 21% of the sarcomas showed PD-L1 expression in both the tumor microenvironment and tumor cells; and kaposi sarcoma, not surprisingly, was the most common sarcoma with 80% of the cases showing this phenotype (14). This high level of co-expression could be attributed to the phenomenal role of the immune system on the development and regression of this tumor.…”

Programmed death ligand 1 (PD-L1) expression influences the immune-tolerogenic microenvironment in antiretroviral therapy-refractory Kaposi's sarcoma: A pilot study

“…In contrast to these findings, a second case-series of sarcomas including five KS samples has shown high prevalence of PD-L1 expression in 80% of KS patients. 22 However, in both studies, cases were collected retrospectively and were not selected according to any specific patient or disease characteristics, which is likely to account for the high inter-study heterogeneity in PD-L1 expression.…”

Development of Checkpoint Inhibitors for Sarcomas

“…66 67 Nevertheless, it is important to highlight that using the expression of PD-L1 as a biomarker encases a series of challenges and unascertained aspects. While early clinical development of anti-PD-1 agents already suggested a correlation between PD-L1 expression and response to therapy, 16 this correlation is imperfect.…”