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<p>Limited biomarker availability hinders the accurate prognostication of individual responses to immunotherapy in gastric cancer (GC). Mature tertiary lymphoid structures (mTLS) substantially affect immunotherapeutic efficacy in patients. However, the inherent limitations of tissue size in gastroscopic biopsies necessitate the development of a new mTLS marker-based classification strategy. An integrated analysis of multimodal data, including GC tissues collected from seven independent medical centers, single-cell transcriptomes, spatial transcriptomics, and transcriptome sequencing, revealed mTLS as a key site for somatic hypermutation and clonal selection in the infiltrating plasma cells of GC. An MZB1 positive score (MPS) was established based on the different degree of plasma cell infiltration between mTLS-positive (mTLS-Po) and mTLS-negative (mTLS-Ne) tumors characterizing MPS<sup>High</sup> and MPS<sup>Low</sup> statuses, respectively. MPS<sup>High</sup> status and combined positive score ≥ 5 indicated a favorable outcome for anti-PD-1 therapy. Conclusively, MPS offers a valuable quantitative approach for improving clinical outcomes and guiding treatment decisions in GC.</p>

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Intratumoral plasma cells predict patient prognosis and responsiveness to neoadjuvant immunotherapy in advanced gastric cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月27日

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  • Jia-Bin Wang,
  • Chen-Yang Jiang,
  • Yin-Hua Ye,
  • You-Xin Gao,
  • Qiao-Ling Zheng,
  • Hua-You Luo,
  • Shuan-Hu Wang,
  • Tao Zhang,
  • Qin-Wen Jin,
  • Chao-Hui Zheng,
  • Ping Li,
  • Jian-Xian Lin,
  • Qi-Yue Chen,
  • Long-Long Cao,
  • Ying-Hong Yang,
  • Chang-Ming Huang,
  • Jian-Wei Xie

摘要

Limited biomarker availability hinders the accurate prognostication of individual responses to immunotherapy in gastric cancer (GC). Mature tertiary lymphoid structures (mTLS) substantially affect immunotherapeutic efficacy in patients. However, the inherent limitations of tissue size in gastroscopic biopsies necessitate the development of a new mTLS marker-based classification strategy. An integrated analysis of multimodal data, including GC tissues collected from seven independent medical centers, single-cell transcriptomes, spatial transcriptomics, and transcriptome sequencing, revealed mTLS as a key site for somatic hypermutation and clonal selection in the infiltrating plasma cells of GC. An MZB1 positive score (MPS) was established based on the different degree of plasma cell infiltration between mTLS-positive (mTLS-Po) and mTLS-negative (mTLS-Ne) tumors characterizing MPSHigh and MPSLow statuses, respectively. MPSHigh status and combined positive score ≥ 5 indicated a favorable outcome for anti-PD-1 therapy. Conclusively, MPS offers a valuable quantitative approach for improving clinical outcomes and guiding treatment decisions in GC.