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. 2017 Jul 5;8(11):2018-2025.
doi: 10.7150/jca.18683. eCollection 2017.

PD-L1 Expression Is Associated with FOXP3+ Regulatory T-Cell Infiltration of Soft Tissue Sarcoma and Poor Patient Prognosis

Yi Que  1 , Wei Xiao  1 , Yuan-Xiang Guan  2 , Yao Liang  2 , Shu-Mei Yan  3 , Huo-Ying Chen  1 , Qiao-Qiao Li  4 , Bu-Shu Xu  1 , Zhi-Wei Zhou  2 , Xing Zhang  1
Affiliations

PD-L1 Expression Is Associated with FOXP3+ Regulatory T-Cell Infiltration of Soft Tissue Sarcoma and Poor Patient Prognosis

Yi Que et al. J Cancer. .

Abstract

Background: Programmed death ligand-1(PD-L1) functions as a negative mediator of immune response through different pathways in anti-tumor immunity. Recent studies have reported that PD-L1 plays a pivotal role in the function of regulatory T-cells (Tregs). Although increases in FOXP3+ Tregs infiltration and PD-L1 expression have been revealed in several cancers, their correlation with soft tissue sarcoma remains unknown. Methods: We included 163 cases of soft tissue sarcoma who were diagnosed and underwent extensive and radical resection at the Sun Yat-sen University Cancer Center, Guangzhou, China, from 2000-2010. PD-L1 and FOXP3 expression was evaluated by immunohistochemistry. Correlation between their expressions and associations with clinicopathological features were studied. Results: Among 163 STS samples, 19 (11.7%) exhibited PD-L1 positivity, and 41 (25.2%) cases expressed high FOXP3+ Treg infiltration. Significant correlation between PD-L1 expression and FOXP3+Treg infiltration in STS was identified (r=0.450, p<0.001). In univariate analysis, PD-L1 expression was significantly associated with high tumor grade and the age of patients, while the presence of FOXP3+ in tumor infiltrating Tregs was significantly associated with the age of patients, high tumor stage, higher tumor grade and tumor depth. Multivariate analysis revealed PD-L1 and FOXP3 as independent prognostic indicators significantly associated with OS and DFS. Conclusions: Our study revealed that PD-L1 and FOXP3+Tregs may work synergistically in promoting immune evasion of the tumors in soft tissue sarcoma. A combined strategy to block PD-L1/PD-1 with simultaneous depletion of Tregs may show promise in enhancing the therapeutic efficacy of these patients.

Keywords: FOXP3+; PD-L1; Soft tissue sarcoma; prognosis.

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Conflict of interest statement

Competing Interests: We declare no conflicts of interest.

Figures

Figure 1
Figure 1
Immunohistochemical expression of PD-L1 in undifferentiated pleomorphic sarcoma(A), synovial sarcoma(B), rhabdomyosarcoma(C) and FOXP3+ infiltration Tregs in undifferentiated pleomorphic sarcoma(D), synovial sarcoma(E), rhabdomyosarcoma(F) Original magnification, 400 x.
Figure 2
Figure 2
Kaplan-Meier survival analysis in soft-tissue sarcomas. Overall survival and disease-free survival according to expression of PD-L1 (A,B), FOXP3 (C,D)and the combined expression pattern of PD-L1 and FOXP3 (PD-L1/FOXP3) (E,F).
Figure 3
Figure 3
Overall survival analysis in undifferentiated pleomorphic sarcoma patients according to expression of PD-L1 (A), FOXP3 (B)and the combined expression pattern of PD-L1 and FOXP3 (PD-L1/FOXP3) (C).
Figure 4
Figure 4
Correlation of PD-L1 and FOXP3 RNA expression in sarcoma
See this image and copyright information in PMC

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