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非小细胞肺癌的空间分析为肿瘤发生和免疫治疗反应提供了深入了解。

Spatial profiling of non-small cell lung cancer provides insights into tumorigenesis and immunotherapy response.

机构信息

Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

Commun Biol. 2024 Aug 2;7(1):930. doi: 10.1038/s42003-024-06568-w.

DOI:10.1038/s42003-024-06568-w
PMID:39095464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11297140/
Abstract

Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths. Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases. This study aims to identify molecular changes in non-small cell lung cancer (NSCLC) patients based on their response to treatment. Using tumor and matched immune cell rich peritumoral tissues, we perform a retrospective, comprehensive spatial transcriptomic analysis of a proven malignant NSCLC sample treated with immune checkpoint inhibitor (ICI). In addition to T cells, other immune cell types, such as B cells and macrophages, were also activated in responders to ICI treatment. In particular, B cells and B cell-mediated immunity pathways are consistently found to be activated. Analysis of the histologic subgroup (lung squamous cell carcinoma, LUSC; lung adenocarcinoma, LUAD) of NSCLC also confirms activation of B cell mediated immunity. Analysis of B cell subtypes shows that B cell subtypes were more activated in immune cell-rich tissues near tumor tissue. Furthermore, increased expression of B cell immunity-related genes is associated with better prognosis. These findings provide insight into predicting ICI treatment responses and identifying appropriate candidates for immunotherapy in NSCLC patients.

摘要

肺癌是全球第二大常见癌症，也是癌症相关死亡的主要原因。尽管靶向治疗和免疫治疗取得了进展，但预后仍然不佳，特别是在转移性病例中。本研究旨在根据非小细胞肺癌（NSCLC）患者对治疗的反应来识别分子变化。我们使用肿瘤和匹配的富含免疫细胞的肿瘤周围组织，对经免疫检查点抑制剂（ICI）治疗的已确诊恶性 NSCLC 样本进行回顾性、全面的空间转录组学分析。除 T 细胞外，其他免疫细胞类型，如 B 细胞和巨噬细胞，也在 ICI 治疗的应答者中被激活。特别是 B 细胞和 B 细胞介导的免疫途径被一致发现被激活。对 NSCLC 的组织学亚组（肺鳞状细胞癌，LUSC；肺腺癌，LUAD）的分析也证实了 B 细胞介导的免疫被激活。B 细胞亚型分析表明，B 细胞亚型在靠近肿瘤组织的富含免疫细胞的组织中更活跃。此外，B 细胞免疫相关基因的表达增加与更好的预后相关。这些发现为预测 ICI 治疗反应和确定 NSCLC 患者免疫治疗的合适候选者提供了深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/aaec0c500154/42003_2024_6568_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/7e98942180e4/42003_2024_6568_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/8c54e2310204/42003_2024_6568_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/40944c3b11ac/42003_2024_6568_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/9faa7594f220/42003_2024_6568_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/79276ad6de94/42003_2024_6568_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/aaec0c500154/42003_2024_6568_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/7e98942180e4/42003_2024_6568_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/8c54e2310204/42003_2024_6568_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/40944c3b11ac/42003_2024_6568_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/9faa7594f220/42003_2024_6568_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/79276ad6de94/42003_2024_6568_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4654/11297140/aaec0c500154/42003_2024_6568_Fig6_HTML.jpg

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