1. Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome
- Author
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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, and Mariana Boroni
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Science - Abstract
Abstract 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.
- Published
- 2024
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