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The underlying determinants governing heterogeneous responses to NACI regimens remain poorly understood, particularly regarding how dynamic tumor-immune interactions shape therapeutic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We characterized microenvironmental dynamics in patients with LACC by integrating single-cell RNA sequencing (RNA-seq), single-cell VDJ sequencing (n=10, five paired pre-NACI\/post-NACI samples) and spatial transcriptomics (ChiCTR2300072535). Pathological response was assessed using major pathological response criteria. The findings were validated in an independent NACI cohort (n=23 with RNA-seq), multiplex immunohistochemistry (mIHC) analysis of six surgically resected specimens, as well as functional in vitro and murine models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MPR patients exhibited cytotoxic revival via oligoclonal expansion of tumor-reactive CD8+T\u2009cell clones and CCR5-mediated myeloid-T cell crosstalk. Conversely, non-MPR tumors exhibited endoplasmic reticulum (ER) stress-adapted DTP cells with elevated ER stress signaling, accompanied by a deficiency in tumor-specific T-cell clone expansion and an accumulation of transforming growth factor beta receptor 2 (TGFBR2) + myeloid\u2009DTP niches. Mechanistically, ER stress signaling via the inositol\u2011requiring enzyme 1 alpha (IRE1\u03b1) \/ X\u2011box binding protein 1 (XBP1) axis induces growth differentiation factor 15 (GDF15) production in DTP cells, contributing to treatment\u2011resistant microdomains. Pharmacological IRE1\u03b1 inhibition synergized with chemoimmunotherapy to eradicate DTP populations in murine models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides critical insights that NACI resistance stems from adaptive ER stress signaling in DTP cells and spatially organized immunosuppressive networks. Targeting the IRE1\u03b1\/XBP1-GDF15 axis represents an actionable strategy to reprogram microenvironmental ecology and improve immunotherapy outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012630","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T17:40:17Z","timestamp":1763574017000},"page":"e012630","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Oligoclonal tumor-specific CD8 T-cell revival and IRE1\u03b1\/XBP1-GDF15-mediated immunosuppressive niches determine neoadjuvant chemoimmunotherapy efficacy in cervical cancer"],"prefix":"10.1136","volume":"13","author":[{"given":"Guangxu","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 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