Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma.
Hidekazu OyoshiJunyan DuShunsuke A SakaiRiu YamashitaMasayuki OkumuraAtsushi MotegiHidehiro HojoMasaki NakamuraHidenari HirataHironori SunakawaDaisuke KotaniTomonori YanoTakashi KojimaYuka NakamuraMotohiro KojimaAyako SuzukiJunko ZenkohKatsuya TsuchiharaTetsuo AkimotoAtsushi ShibataYutaka SuzukiShun-Ichiro KageyamaPublished in: Science advances (2023)
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.
Keyphrases
- single cell
- rna seq
- genome wide
- immune response
- gene expression
- high throughput
- genome wide identification
- combination therapy
- induced apoptosis
- dna methylation
- early stage
- dendritic cells
- acute myeloid leukemia
- drug induced
- radiation therapy
- bone marrow
- high glucose
- liver injury
- diabetic rats
- copy number
- squamous cell carcinoma
- genome wide analysis
- endoplasmic reticulum stress
- oxidative stress
- endothelial cells
- locally advanced
- cell proliferation
- pi k akt
- real time pcr