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

doi:10.1016/j.isci.2023.106480

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

iScience. 2023 Mar 21;26(4):106480. doi: 10.1016/j.isci.2023.106480. eCollection 2023 Apr 21.

Authors

Sho Okuda¹, Kenoki Ohuchida¹, Shoichi Nakamura¹, Chikanori Tsutsumi¹, Kyoko Hisano¹, Yuki Mochida¹, Jun Kawata², Yoshiki Ohtsubo¹, Tomohiko Shinkawa¹, Chika Iwamoto¹, Nobuhiro Torata¹, Yusuke Mizuuchi¹, Koji Shindo¹, Taiki Moriyama¹, Kohei Nakata¹, Takehiro Torisu³, Takashi Morisaki⁴, Takanari Kitazono³, Yoshinao Oda², Masafumi Nakamura¹

Affiliations

¹ Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
² Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu Hospital, Fukuoka 812-8582, Japan.
³ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
⁴ Department of Cancer Immunotherapy, Fukuoka General Cancer Clinic, Fukuoka 812-0018, Japan.

Abstract

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.

Keywords: Cancer; Immunology; Transcriptomics.