Synergistic induction of tertiary lymphoid structures by chemoimmunotherapy in bladder cancer

作者：Lu Zhang, Ruiyun Zhang, Di Jin, Tianxiang Zhang, Akezhouli Shahatiaili, Jingyu Zang, Lu Wang, Yuanchun Pu, Guanglei Zhuang, Haige Chen, Jinhai Fan · 发表于：British Journal of Cancer · 年份：2024 · DOI：10.1038/s41416-024-02598-7 · 被引用次数：25 · 研究领域：Single-cell and spatial transcriptomics、Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers

BACKGROUND: A substantial number of patients with bladder cancer fail to benefit from immune checkpoint inhibitors (ICIs). We aim to investigate whether the addition of other therapeutic modalities into immunotherapy may augment the immune reactivity, thereby improving the overall response rate. METHODS: We conducted a comprehensive assessment of the immunological changes following immunotherapy and chemotherapy, employing both single-cell RNA sequencing and bulk RNA sequencing analyses. RESULTS: The bladder cancer patient treated with ICIs exhibited a higher abundance of B cells and T follicular helper cells compared to the treatment-naïve patient. Analysis of public datasets and the in-house RJBLC-I2N003 cohort revealed the induction of tertiary lymphoid structure (TLS) neogenesis and maturation by immunotherapy. The IMvigor 210 study suggested that TLS could serve as a predictor of immunotherapy response and patient prognosis. In addition, genome-wide transcriptome data unveiled a shift towards the immune-enriched subtype over the desert subtype in patients receiving neoadjuvant chemotherapy. Notably, the proportions of CD20 + B cells, T follicular helper cells, and TLSs were significantly increased. In patients treated with a combination of neoadjuvant chemotherapy and ICIs, TLS positivity and maturity were improved compared to the baseline. Furthermore, neoadjuvant chemoimmunotherapy resulted in a higher rate of pathological complete response compared to monotherapies. C...