Clonal Expansion of Tumor-Infiltrating T Cells and Analysis of the Tumor Microenvironment within Esophageal Squamous Cell Carcinoma Relapsed after Definitive Chemoradiation Therapy.

Takahiro Mori,Keisuke Nasu,Ryuji Suzuki,Takamasa Yoshizawa,Koji Kuwano,Kenichi Kumagai,Yoshiki Hamada,Hideki Kanazawa

doi:10.3390/ijms22031098

Abstract

(1) Background: Comparable prognoses after definitive chemoradiation therapy (CRT) to surgery alone for esophageal squamous cell carcinoma (ESCC) have been previously reported; however, no robust prognostic markers have been established. The clonality of tumor-infiltrating lymphocytes (TILs) and tumor microenvironments (TMEs) in ESCC relapsed after CRT were examined to explore prognostic markers. (2) Methods: Clonality of TIL and TME were examined in ESCC with and without preceding CRT, as well as oral squamous cell carcinoma (OSCC) and healthy volunteers as controls. The clonality of TIL was assessed by T-cell receptor (TCR) α and β repertoire analyses and evaluated by diversity indices. The TME was assessed by quantitative polymerase chain reaction evaluating PD-L1 and CD8B. (3) Results: The clonal expansion of TIL was significantly induced within ESCCs and OSCCs, when compared to healthy volunteers, and was mostly induced within ESCCs after definitive CRT. Diversity indices of TIL were not associated with the prognosis, but the ratio of PD-L1 mRNA to CD8B mRNA in TME was significantly associated with a poor prognosis after salvage surgery (p = 0.007). (4) Conclusions: The clonal expansion of TIL is induced after definitive CRT for ESCC, and the ratio of PD-L1 mRNA to CD8B mRNA within tumor tissues is a prognostic marker candidate for salvage esophagectomy after CRT.

Highlights

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal neoplasms in both Japan and other parts of the world [1,2,3]
We reveal the results of diversity analyses of the T-cell receptor (TCR) repertoire of tumor-infiltrating lymphocytes (TILs) within post-definitive chemoradiation therapy (CRT) locally relapsed ESCC by comparing them to ESCC and oral squamous cell carcinoma (OSCC) that have both been treated only by surgery in order to reveal the specific immunological features initiated by definitive CRT
We demonstrate the molecular features of the tumor microenvironments (TMEs), especially in ESCCs relapsed after definitive CRT, which could be prognostic marker candidates after salvage esophagectomy

Summary

Introduction

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal neoplasms in both Japan and other parts of the world [1,2,3]. Multimodal medical treatments consisting of neoadjuvant chemotherapy or chemoradiation therapy followed by surgery is the current gold standard of treatment, especially for patients with advanced stage II or III ESCCs [4,5,6]. Definitive chemoradiation therapy (CRT) itself may be another powerful treatment for carcinoma curability, because some cases have been reported to achieve pathologically complete remission (pCR) after neoadjuvant CRT [7]. It is necessary to treat them using the optimal medical procedures that have been determined by robust predictive or prognostic markers. Various studies have been performed to identify the predictive or prognostic factors of medical procedures for ESCC, including CRT, no robust marker has yet been established [11,12,13]

Methods

Results

Conclusion