Abstract
Recently, the possibility of PD1 pathway-targeted therapy has been extensively studied in various human malignant tumors. However, no previous study has investigated their potential application for soft-tissue sarcomas (STS). In this study, we evaluated the clinical impact of intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression in tumor cells in 105 cases of STS. Intra-tumoral infiltration of PD1-positive lymphocytes and PD-L1 expression were seen in 65% and 58% of STS, respectively. Both PD1-positivity and PD-L1 expression were significantly associated with advanced clinicopathological parameters such as higher clinical stage, presence of distant metastasis, higher histological grade, poor differentiation of tumor, and tumor necrosis. Moreover, both PD1-positivity and PD-L1 positivity were independent prognostic indicators of overall survival (OS) and event-free survival (EFS) of STS by multivariate analysis. In addition, the combined pattern of PD1- and PD-L1-positivity was also an independent prognostic indicator for OS and EFS by multivariate analysis. The patents with a PD1+/PD-L1+ pattern had the shortest survival time. In conclusion, this study is the first to demonstrate that the infiltration of PD1 positive lymphocytes and PD-L1 expression in STS cells could be used as novel prognostic indicators for STS. Moreover, the evaluation of PD1- and PD-L1-positivity in STS is also available as possible criteria for selection of patients suitable for PD1-based immunotherapy.
Highlights
Programmed death 1 (PD1) is a member of the CD28 receptor family and attenuates immune responses by negatively regulating T-cell proliferation and function [1,2]
The association of PD1- or programmed death 1 ligand 1 (PD-L1)-positivity with variable clinicopathological factors of soft-tissue sarcomas (STS) is summarized in Table 1 and Table 2
PD-L1 expressing tumor cells escape from the lysis by activated T lymphocytes [31] and the expression of PD-L1 in tumor cells associated with progression of human malignant tumors [9,10,13,14,15,16,17]
Summary
Programmed death 1 (PD1) is a member of the CD28 receptor family and attenuates immune responses by negatively regulating T-cell proliferation and function [1,2]. The PD1/PD-L1 interaction attenuates the immune response by decreasing cytokine production [4,5] and inducing T lymphocyte anergy and apoptosis [6,7]. The expression rate of PD-L1 in human malignant tumors has been reported to vary from 19% to 92%. Based on the prognostic impact of the infiltration of PD1-positive lymphocytes and PD-L1 expression in human cancers, PD1 has been put forth as a novel target for immunotherapy of human malignant tumors [8,22,23,24,25]. Recent preliminary data from clinical trials targeting the PD1-pathway showed response rates of 18 - 31% in human cancers [22,23]
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