The Single-Cell Immunogenomic Landscape of B and Plasma Cells in Early-Stage Lung Adenocarcinoma
| العنوان: | The Single-Cell Immunogenomic Landscape of B and Plasma Cells in Early-Stage Lung Adenocarcinoma |
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| المؤلفون: | Dapeng Hao, Guangchun Han, Ansam Sinjab, Lorena Isabel Gomez-Bolanos, Rossana Lazcano, Alejandra Serrano, Sharia D. Hernandez, Enyu Dai, Xuanye Cao, Jian Hu, Minghao Dang, Ruiping Wang, Yanshuo Chu, Xingzhi Song, Jianhua Zhang, Edwin R. Parra, Jennifer A. Wargo, Stephen G. Swisher, Tina Cascone, Boris Sepesi, Andrew P. Futreal, Mingyao Li, Steven M. Dubinett, Junya Fujimoto, Luisa M. Solis Soto, Ignacio I. Wistuba, Christopher S. Stevenson, Avrum Spira, Shabnam Shalapour, Humam Kadara, Linghua Wang |
| المصدر: | Cancer Discov |
| بيانات النشر: | American Association for Cancer Research (AACR), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Lung Neoplasms, Oncology, Plasma Cells, Humans, Adenocarcinoma of Lung, Adenocarcinoma, Prognosis, Article, Ecosystem |
| الوصف: | Tumor-infiltrating B and plasma cells (TIB) are prevalent in lung adenocarcinoma (LUAD); however, they are poorly characterized. We performed paired single-cell RNA and B-cell receptor (BCR) sequencing of 16 early-stage LUADs and 47 matching multiregion normal tissues. By integrative analysis of ∼50,000 TIBs, we define 12 TIB subsets in the LUAD and adjacent normal ecosystems and demonstrate extensive remodeling of TIBs in LUADs. Memory B cells and plasma cells (PC) were highly enriched in tumor tissues with more differentiated states and increased frequencies of somatic hypermutation. Smokers exhibited markedly elevated PCs and PCs with distinct differentiation trajectories. BCR clonotype diversity increased but clonality decreased in LUADs, smokers, and with increasing pathologic stage. TIBs were mostly localized within CXCL13+ lymphoid aggregates, and immune cell sources of CXCL13 production evolved with LUAD progression and included elevated fractions of CD4 regulatory T cells. This study provides a spatial landscape of TIBs in early-stage LUAD.Significance:While TIBs are highly enriched in LUADs, they are poorly characterized. This study provides a much-needed understanding of the transcriptional, clonotypic states and phenotypes of TIBs, unraveling their potential roles in the immunopathology of early-stage LUADs and constituting a road map for the development of TIB-targeted immunotherapies for the treatment of this morbid malignancy.This article is highlighted in the In This Issue feature, p. 2483 |
| تدمد: | 2159-8290 2159-8274 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b2d902968d41a7c6cdadf3ec923aba3 https://doi.org/10.1158/2159-8290.cd-21-1658 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7b2d902968d41a7c6cdadf3ec923aba3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21598290 21598274 |
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