PD-L1 and CD4 are independent prognostic factors for overall survival in endometrial carcinomas

Shuang Zhang,Toyomi Satoh,Nan Qi,Hiroyuki Ochi,Azusa Akiyama,Hiroya Itagaki,Takeo Minaguchi,Nobutaka Tasaka,Ayumi Shikama,Manabu Sakurai,Chenyang Xu

doi:10.1186/s12885-020-6545-9

Abstract

BackgroundTumor microenvironment (TME) including the immune checkpoint system impacts prognosis in some types of malignancy. The aim of our study was to investigate the precise prognostic significance of the TME profile in endometrial carcinoma.MethodsWe performed immunohistochemistry of the TME proteins, PD-L1, PD-1, CD4, CD8, CD68, and VEGF in endometrial carcinomas from 221 patients.ResultsHigh PD-L1 in tumor cells (TCs) was associated with better OS (p = 0.004), whereas high PD-L1 in tumor-infiltrating immune cells (TICs) was associated with worse OS (p = 0.02). High PD-L1 in TICs correlated with high densities of CD8+ TICs and CD68+ TICs, as well as microsatellite instability (p = 0.00000064, 0.00078, and 0.0056), while high PD-L1 in TCs correlated with longer treatment-free interval (TFI) after primary chemotherapy in recurrent cases (p = 0.000043). High density of CD4+ TICs correlated with better OS and longer TFI (p = 0.0008 and 0.014). Univariate and multivariate analyses of prognostic factors revealed that high PD-L1 in TCs and high density of CD4+ TICs were significant and independent for favorable OS (p = 0.014 and 0.0025).ConclusionThe current findings indicate that PD-L1 and CD4+ helper T cells may be reasonable targets for improving survival through manipulating chemosensitivity, providing significant implications for combining immunotherapies into the therapeutic strategy for endometrial carcinoma.

Highlights

Tumor microenvironment (TME) including the immune checkpoint system impacts prognosis in some types of malignancy
Our above observations may be explicable if some proportion of expressed programmed cell deathligand 1 (PD-L1) could move between the surface of tumor cells (TCs) and the surface of tumorinfiltrating immune cells (TICs) so that the PD-L1 bound to Programmed cell death-1 (PD-1) on the surface of TICs may induce adaptive immune resistance leading to poor survival, while the PD-L1 remaining on the surface of TCs may not
We have demonstrated here that high PD-L1 in TCs was associated with better overall survival (OS), while high PD-L1 in TICs was associated with worse OS

Summary

Introduction

Tumor microenvironment (TME) including the immune checkpoint system impacts prognosis in some types of malignancy. The majority of cases are diagnosed at an early stage, and the 5-year survival rate for those with localized disease is 95% [2]. The 5-year survival rate for those with advanced/recurrent measurable disease is < 10%, and the efficacy of second-. Programmed cell death-1 (PD-1), immune inhibiting receptor, is expressed on the surface of activated T cells and B cells, and the PD-1 pathway plays critical roles in maintaining immunological self-tolerance [5]. Tumor cells escape host antitumor immune response through the PD-1/PD-L1 pathway.

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