Neoadjuvant chemotherapy enhances anti-tumor immune response of tumor microenvironment in human esophageal squamous cell carcinoma

Sho Okuda; Kenoki Ohuchida; Shoichi Nakamura; Chikanori Tsutsumi; Kyoko Hisano; Yuki Mochida; Jun Kawata; Yoshiki Ohtsubo; Tomohiko Shinkawa; Chika Iwamoto; Nobuhiro Torata; Yusuke Mizuuchi; Koji Shindo; Taiki Moriyama; Kohei Nakata; Takehiro Torisu; Takashi Morisaki; Takanari Kitazono; Yoshinao Oda; Masafumi Nakamura

iScience (Apr 2023)

Neoadjuvant chemotherapy enhances anti-tumor immune response of tumor microenvironment in human esophageal squamous cell carcinoma

Sho Okuda,
Kenoki Ohuchida,
Shoichi Nakamura,
Chikanori Tsutsumi,
Kyoko Hisano,
Yuki Mochida,
Jun Kawata,
Yoshiki Ohtsubo,
Tomohiko Shinkawa,
Chika Iwamoto,
Nobuhiro Torata,
Yusuke Mizuuchi,
Koji Shindo,
Taiki Moriyama,
Kohei Nakata,
Takehiro Torisu,
Takashi Morisaki,
Takanari Kitazono,
Yoshinao Oda,
Masafumi Nakamura

Affiliations

Sho Okuda: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Kenoki Ohuchida: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Corresponding author
Shoichi Nakamura: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Chikanori Tsutsumi: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Kyoko Hisano: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Yuki Mochida: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Jun Kawata: Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu Hospital, Fukuoka 812-8582, Japan
Yoshiki Ohtsubo: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Tomohiko Shinkawa: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Chika Iwamoto: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Nobuhiro Torata: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Yusuke Mizuuchi: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Koji Shindo: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Taiki Moriyama: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Kohei Nakata: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Takehiro Torisu: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Takashi Morisaki: Department of Cancer Immunotherapy, Fukuoka General Cancer Clinic, Fukuoka 812-0018, Japan
Takanari Kitazono: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Yoshinao Oda: Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu Hospital, Fukuoka 812-8582, Japan
Masafumi Nakamura: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

Journal volume & issue: Vol. 26, no. 4
p. 106480

Abstract

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Summary: Although chemotherapy has been an essential treatment for cancer, the development of immune checkpoint blockade therapy was revolutionary, and a comprehensive understanding of the immunological tumor microenvironment (TME) has become crucial. Here, we investigated the impact of neoadjuvant chemotherapy (NAC) on immune cells in the TME of human esophageal squamous cell carcinoma using single cell RNA-sequencing. Analysis of 30 fresh samples revealed that CD8+/CD4+ T cells, dendritic cells (DCs), and macrophages in the TME of human esophageal squamous cell carcinoma showed higher levels of an anti-tumor immune response in the NAC(+) group than in the NAC(−) group. Furthermore, the immune cells of the NAC(+) group interacted with each other resulting in enhanced anti-tumor immune response via various cytokines, including IFNG in CD8+/CD4+ T cells, EBI3 in DCs, and NAMPT in macrophages. Our results suggest that NAC potentially enhances the anti-tumor immune response of immune cells in the TME.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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