Yuhan Wang

Oligoclonal tumor-specific CD8 T-cell revival and IRE1α/XBP1-GDF15-mediated immunosuppressive niches determine neoadjuvant chemoimmunotherapy efficacy in cervical cancer

Background Neoadjuvant chemoimmunotherapy (NACI) shows promise for locally advanced cervical cancer (LACC), but drug-tolerant persister (DTP) cells and immunosuppressive microenvironmental adaptations limit clinical efficacy. The underlying determinants governing heterogeneous responses to NACI regimens remain poorly understood, particularly regarding how dynamic tumor-immune interactions shape therapeutic outcomes. Methods 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. Results MPR patients exhibited cytotoxic revival via oligoclonal expansion of tumor-reactive CD8+T cell 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 DTP niches. Mechanistically, ER stress signaling via the inositol‑requiring enzyme 1 alpha (IRE1α) / X‑box binding protein 1 (XBP1) axis induces growth differentiation factor 15 (GDF15) production in DTP cells, contributing to treatment‑resistant microdomains. Pharmacological IRE1α inhibition synergized with chemoimmunotherapy to eradicate DTP populations in murine models. Conclusions This study provides critical insights that NACI resistance stems from adaptive ER stress signaling in DTP cells and spatially organized immunosuppressive networks. Targeting the IRE1α/XBP1-GDF15 axis represents an actionable strategy to reprogram microenvironmental ecology and improve immunotherapy outcomes.

The safety and effectiveness of preserving the ascending uterine artery in a modified fertility-sparing abdominal radical trachelectomy

To evaluate the outcome of preserving the ascending uterine artery in a modified fertility-sparing abdominal radical trachelectomy and understand whether preserving uterine arteries during abdominal radical trachelectomy is helpful for patients. From September 2005 to September 2019, 31 early uterine cervical cancer patients who underwent modified fertility-sparing abdominal radical trachelectomy were enrolled in this study, and were followed up in our cancer center. Computed tomography (CT) of the abdomen and pelvis was advised as the initial investigation to evaluate the ascending uterine artery in 11 patients. The major outcomes were recurrence, mortality, CT results and obstetric outcomes. During the median follow-up of 56 months, two recurrences were recorded. Among 11 patients who underwent CT, none of them showed uterine arteries occlusion. Fifteen patients attempted to conceive, and 5 pregnancies were achieved in 5 patients. Hence, the pregnancy rate among patients who attempted to conceive was 33.3 %. There was only one artificial first-trimester abortion. Three pregnancies resulted in live births, and two of them got full-term births. The modified fertility-sparing abdominal radical trachelectomy in preserving uterine arteries is effective, and it is recommended that surgeon should retain the uterine artery as much as possible during operation.