Tumor Infiltrating PD1-Positive Lymphocytes and the Expression of PD-L1 Predict Poor Prognosis of Soft Tissue Sarcomas

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.

Programmed Cell Death 1 (PD-1) and Its Ligand (PD-L1) in Common Cancers and Their Correlation with Molecular Cancer Type

“…Our study revealed a low expression of both PD-1 and PD-L1 in several highly aggressive tumors, including Merkel cell carcinoma, hepatocellular, and pancreatic carcinoma. In contrast, PD-L1 expression was particularly high in dedifferentiated liposarcomas, which is in line with a recent report by Kim and colleagues (17). We also report for the first time the PD-L1 positivity in chondrosarcomas and extraskeletal myxoid chondrosarcomas.…”

T‐cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death‐ligand 1 expression in patients with soft tissue sarcomas

“…1B). Several studies to date have examined the presence or absence of PD‐1 and PD‐L1 in STS samples, but to the best of our knowledge none has scored the level of protein expression based on IHC 31, 32. We stained FFPE sections by IHC and scored them using a scoring system of 0 to ≥ 5 as described above and illustrated in Supporting Information Figure 1.…”

Cytokine Induced Killer cells are effective against sarcoma cancer stem cells spared by chemotherapy and target therapy.

“…Preclinical data in this direction were recently reported in the setting of hematologic malignancies and are likely to be confirmed also in the field of solid tumors. 15,16,50-52 The cytotoxic effect of CIK may promote a “positive” inflammation at tumor sites, with release of tumor antigenic fragments and Th1 cytokines that might in turn promote an adaptive immune response favored by checkpoint inhibitors.…”

“…This is likely due to their relatively minor neo-antigen load and the presence of important immunosuppressive elements in the tumor microenvironment. 15,16 In this field, a promising immunotherapy approach is based on the adoptive infusion of antitumor immune-effectors, with important results recently reported against selected cases of synovial sarcoma treated with anti-NY-ESO1 engineered T lymphocytes. 17-21 …”