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

• Published in: Communications biology 2024-08, Vol.7 (1), p.930-10, Article 930
• Main Authors: Kim, Joon, Yong, Seung Hyun, Jang, Gyuho, Kim, Yumin, Park, Raekil, Koh, Hyun-Hee, Kim, Sehui, Oh, Chang-Myung, Lee, Sang Hoon
• Format: Article
• Language: English
• Subjects: 38/91; 631/250/251; 631/67/1612/1350; Adenocarcinoma; Aged; Biomedical and Life Sciences; Carcinogenesis - genetics; Carcinogenesis - immunology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - therapy; Cell activation; Cell-mediated immunity; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Life Sciences; Lung cancer; Lung carcinoma; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Lymphocytes B; Lymphocytes T; Macrophages; Male; Metastases; Middle Aged; Non-small cell lung carcinoma; Prognosis; Retrospective Studies; Small cell lung carcinoma; Squamous cell carcinoma; Transcription activation; Transcriptome; Transcriptomics; Tumor Microenvironment - immunology; Tumorigenesis
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06568-w

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. This study investigates molecular changes in the response of NSCLC patients to ICI using spatial transcriptomics. Activation of B cellassociated pathways correlates with improved prognosis and guides personalized immunotherapy approaches in NSCLC.