骨髓源性细胞状态的单细胞分辨率表征与癌症结果的关系。
Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome.
发表日期：2024 Jul 07
作者：
Gabriela Rapozo Guimarães, Giovanna Resk Maklouf, Cristiane Esteves Teixeira, Leandro de Oliveira Santos, Nayara Gusmão Tessarollo, Nayara Evelin de Toledo, Alessandra Freitas Serain, Cristóvão Antunes de Lanna, Marco Antônio Pretti, Jéssica Gonçalves Vieira da Cruz, Marcelo Falchetti, Mylla M Dimas, Igor Salerno Filgueiras, Otavio Cabral-Marques, Rodrigo Nalio Ramos, Fabiane Carvalho de Macedo, Fabiana Resende Rodrigues, Nina Carrossini Bastos, Jesse Lopes da Silva, Edroaldo Lummertz da Rocha, Cláudia Bessa Pereira Chaves, Andreia Cristina de Melo, Pedro M M Moraes-Vieira, Marcelo A Mori, Mariana Boroni
来源：
Experimental Hematology & Oncology
摘要：
肿瘤相关骨髓源性细胞（MDC）因其显着的可塑性和致瘤行为而显着影响癌症预后和治疗反应。在这里，我们整合了来自不同癌症类型的单细胞 RNA 测序数据，识别了肿瘤微环境中的 29 个 MDC 亚群。我们的分析揭示了各种肿瘤中异常扩增的 MDC 亚群，并区分了通常分组在一起的细胞状态，例如 TREM2 和 FOLR2 亚群。使用反卷积方法，我们确定了五个亚群作为独立的预后标记，包括共表达 TREM2 和 PD-1、以及 FOLR2 和 PDL-2 的状态。此外，TREM2 单独并不能可靠地预测癌症预后，因为其他 TREM2 巨噬细胞根据局部线索显示出与预后的不同关联。独立队列的验证证实，表达 FOLR2 的巨噬细胞与卵巢癌和三阴性乳腺癌的不良临床结果相关。这份全面的 MDC 图集为进一步分析、推进实体癌治疗策略提供了宝贵的见解和基础。© 2024。作者。
Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.© 2024. The Author(s).