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Article

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

1
Departments of Clinical Oncology and Gastroenterological Surgery, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan
2
Department of Rheumatology and Clinical Immunology, Clinical Research Center for Rheumatology and Allergy, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0385, Japan
3
Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai 980-8574, Japan
4
Department of Oral-Maxillofacial Surgery and Orthodontics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
5
Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan
6
Department of Surgery, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Lukas J. A. C. Hawinkels
Int. J. Mol. Sci. 2021, 22(3), 1098; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031098
Received: 24 December 2020 / Revised: 7 January 2021 / Accepted: 19 January 2021 / Published: 22 January 2021
(This article belongs to the Special Issue Recent Advances in Biotechnology)
(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. View Full-Text
Keywords: esophageal squamous cell carcinoma; definitive chemoradiation therapy; tumor-infiltrating T cell; TCR repertoire; PD-L1; CD8; salvage esophagectomy; prognostic marker esophageal squamous cell carcinoma; definitive chemoradiation therapy; tumor-infiltrating T cell; TCR repertoire; PD-L1; CD8; salvage esophagectomy; prognostic marker
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MDPI and ACS Style

Mori, T.; Kumagai, K.; Nasu, K.; Yoshizawa, T.; Kuwano, K.; Hamada, Y.; Kanazawa, H.; Suzuki, R. Clonal Expansion of Tumor-Infiltrating T Cells and Analysis of the Tumor Microenvironment within Esophageal Squamous Cell Carcinoma Relapsed after Definitive Chemoradiation Therapy. Int. J. Mol. Sci. 2021, 22, 1098. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031098

AMA Style

Mori T, Kumagai K, Nasu K, Yoshizawa T, Kuwano K, Hamada Y, Kanazawa H, Suzuki R. Clonal Expansion of Tumor-Infiltrating T Cells and Analysis of the Tumor Microenvironment within Esophageal Squamous Cell Carcinoma Relapsed after Definitive Chemoradiation Therapy. International Journal of Molecular Sciences. 2021; 22(3):1098. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031098

Chicago/Turabian Style

Mori, Takahiro, Kenichi Kumagai, Keisuke Nasu, Takamasa Yoshizawa, Koji Kuwano, Yoshiki Hamada, Hideki Kanazawa, and Ryuji Suzuki. 2021. "Clonal Expansion of Tumor-Infiltrating T Cells and Analysis of the Tumor Microenvironment within Esophageal Squamous Cell Carcinoma Relapsed after Definitive Chemoradiation Therapy" International Journal of Molecular Sciences 22, no. 3: 1098. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031098

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