TY - JOUR
T1 - Neoadjuvant chemotherapy enhances anti-tumor immune response of tumor microenvironment in human esophageal squamous cell carcinoma
AU - Okuda, Sho
AU - Ohuchida, Kenoki
AU - Nakamura, Shoichi
AU - Tsutsumi, Chikanori
AU - Hisano, Kyoko
AU - Mochida, Yuki
AU - Kawata, Jun
AU - Ohtsubo, Yoshiki
AU - Shinkawa, Tomohiko
AU - Iwamoto, Chika
AU - Torata, Nobuhiro
AU - Mizuuchi, Yusuke
AU - Shindo, Koji
AU - Moriyama, Taiki
AU - Nakata, Kohei
AU - Torisu, Takehiro
AU - Morisaki, Takashi
AU - Kitazono, Takanari
AU - Oda, Yoshinao
AU - Nakamura, Masafumi
N1 - Funding Information:
The authors would like to thank E. Manabe and S. Sadatomi (Department of Surgery and Oncology, Kyushu University Hospital, Fukuoka, Japan) for their technical assistance during experiments. The computation was carried out using the computer resource offered under the category of general projects by Research Institute for Information Technology, Kyushu University. This work was supported by JSPS KAKENHI Grant Numbers JP19H03732, JP20K17621, JP20K17622, JP21K08800, JP21K19530, and JP21K19531. We thank Gabrielle White Wolf, PhD, from Edanz (https://www.edanz.com/) for editing a draft of this manuscript. S.O.: Conceptualization, data curation, formal analysis, investigation, methodology, project administration, software, visualization, and writing – original draft. K.O.: Conceptualization, formal analysis, funding acquisition, methodology, project administration, resources, supervision, and writing – review & editing. S.N.: Data curation, formal analysis, investigation, methodology, software, validation, and visualization. C.T.: Data curation, formal analysis, investigation, methodology, software, validation, and visualization. K.H.: Data curation, formal analysis, investigation, methodology, software, validation, and visualization. Y.M.: Methodology and validation. J.K.: Resources. Y.O.: Data curation, formal analysis, investigation, methodology, software, validation, and visualization. T.S.: Investigation and validation. C.I.: Investigation, methodology, and validation. N.T.: Formal analysis, funding acquisition, and software. Y.M.: Funding acquisition and project administration. K.S.: Project administration and resources. T.M.: Funding acquisition, project administration, resources, and supervision. K.N.: Project administration and supervision. T.T.: Resources, supervision, and writing – review & editing. T.M.: Supervision and writing – review & editing. T.K.: Resources, supervision, and writing – review & editing. Y.O.: Resources, supervision, and writing – review & editing. M.N.: Conceptualization, funding acquisition, supervision, and writing – review & editing. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.
Funding Information:
The authors would like to thank E. Manabe and S. Sadatomi (Department of Surgery and Oncology, Kyushu University Hospital, Fukuoka, Japan) for their technical assistance during experiments. The computation was carried out using the computer resource offered under the category of general projects by Research Institute for Information Technology, Kyushu University. This work was supported by JSPS KAKENHI Grant Numbers JP19H03732 , JP20K17621 , JP20K17622 , JP21K08800 , JP21K19530 , and JP21K19531 . We thank Gabrielle White Wolf, PhD, from Edanz ( https://www.edanz.com/ ) for editing a draft of this manuscript.
Publisher Copyright:
© 2023 The Authors
PY - 2023/4/21
Y1 - 2023/4/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85151494464&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151494464&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.106480
DO - 10.1016/j.isci.2023.106480
M3 - Article
AN - SCOPUS:85151494464
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 4
M1 - 106480
ER -
