Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Science advances - 9(2023), 50 vom: 15. Dez., Seite eadh9069 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Oyoshi, Hidekazu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 10.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/sciadv.adh9069 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365821217 |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Yamashita, Riu |e verfasserin |4 aut | |
| 700 | 1 | |a Okumura, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Motegi, Atsushi |e verfasserin |4 aut | |
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| 700 | 1 | |a Nakamura, Masaki |e verfasserin |4 aut | |
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