학술논문
Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma.
Document Type
Article
Author
Hidekazu Oyoshi; Junyan Du; Sakai, Shunsuke A.; Riu Yamashita; Masayuki Okumura; Atsushi Motegi; Hidehiro Hojo; Masaki Nakamura; Hidenari Hirata; Hironori Sunakawa; Daisuke Kotani; Tomonori Yano; Takashi Kojima; Yuka Nakamura; Motohiro Kojima; Ayako Suzuki; Junko Zenkoh; Katsuya Tsuchihara; Tetsuo Akimoto; Atsushi Shibata
Source
Subject
*PROGRAMMED cell death 1 receptors
*SQUAMOUS cell carcinoma
*ESOPHAGEAL tumors
*GENE expression profiling
*MYELOID cells
*MACROPHAGES
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Language
ISSN
2375-2548
Abstract
Radiotherapy (RT) combined with immunotherapy is promising; however, the immune response signature in the clinical setting after RT remains unclear. Here, by integrative spatial and single-cell analyses using multiplex immunostaining (CODEX), spatial transcriptome (VISIUM), and single-cell RNA sequencing, we substantiated the infiltration of immune cells into tumors with dynamic changes in immunostimulatory and immunosuppressive gene expression after RT. In addition, our comprehensive analysis uncovered time- and cell type-dependent alterations in the gene expression profile after RT. Furthermore, myeloid cells showed prominent up-regulation of immune response-associated genes after RT. Notably, a subset of infiltrating tumor-associated myeloid cells showing PD-L1 positivity exhibited significant up-regulation of immunostimulatory (HMGB1 and ISG15), immunosuppressive (SIRPA and IDO1), and protumor genes (CXCL8, CCL3, IL-6, and IL-1AB), which can be targets of immunotherapy in combination with PD-L1. These datasets will provide information on the RT-induced gene signature to seek an appropriate target for personalized immunotherapy combined with RT and guide the timing of combination therapy. [ABSTRACT FROM AUTHOR]