S2549
Radiobiology - Microenvironment
ESTRO 2026
validated in TCGA-CESC and CGCI cohorts. To localize gene expression at the cellular level, six additional biopsies underwent single-cell RNA sequencing (scRNA-seq). Results: Bulk transcriptomic profiling revealed that non- responders exhibited enrichment of neutrophil chemotaxis, TNF/IL-17 signaling, and angiogenesis, whereas responders showed activation of B-cell and immunoglobulin pathways. Immune deconvolution demonstrated increased neutrophil infiltration, higher checkpoint expression (PD-L1, CTLA4, LAG3, TIGIT), and elevated stromal and immune scores in non- responders. A three-gene signature (BCAT1, ITGA5, CXCL2) predicted poor survival and reflected myeloid– endothelial activation. scRNA-seq confirmed that BCAT1 and ITGA5 were mainly expressed in myeloid cells, while CXCL2 was confined to endothelial cells, highlighting a neutrophil–angiogenesis feedback axis that sustains an immunosuppressive microenvironment.
Figure 2. Single-cell RNA-seq confirms myeloid expression of ITGA5/BCAT1 and endothelial localization of CXCL2, validating the myeloid– endothelial resistance axis. Conclusion: Integrated bulk and single-cell analyses uncover a myeloid–endothelial crosstalk that underlies resistance to CCRT + ICI in cervical cancer. Neutrophil- driven inflammation and endothelial activation jointly shape a pro-tumor TME. Targeting this axis through myeloid or anti-angiogenic modulation may enhance response to chemo-radio-immunotherapy and inform future biomarker-guided trials.The study protocol was approved by the Ethics Committee of Tianjin Medical University Cancer Institute & Hospital (Approval Number: E2020605).The raw sequence data have been deposited in the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation (GSA-Human: HRA006417 and HRA006447) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa-human. References: 1. Tewari KS et al. Survival with Cemiplimab in recurrent cervical cancer. N Engl J Med 20222. Colombo N et al. Pembrolizumab plus chemoradiotherapy in locally advanced cervical cancer (KEYNOTE-A18). Lancet Oncol 20253. Tewari KS et al. Durvalumab concurrent chemoradiotherapy for locally advanced cervical cancer (CALLA). Lancet Oncol 20244. de Andrade LF et al. Immune microenvironment and biomarkers of radioresistance in cervical cancer. Front Immunol 20235. Demaria S, Formenti SC. The abscopal effect and radiotherapy-induced immune modulation. Nat Rev Clin Oncol 20236. Jiang Y et al. Multi-omics dissection of tumor microenvironment identifies myeloid–endothelial crosstalk mediating immune
Figure 1. Bulk RNA-seq and immune deconvolution reveal neutrophil-driven inflammation and angiogenesis in non-responders versus B-cell enrichment in responders.
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