Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome.
Gabriela Rapozo GuimarãesGiovanna Resk MakloufCristiane Esteves TeixeiraLeandro de Oliveira SantosNayara Gusmão TessarolloNayara Evelin de ToledoAlessandra Freitas SerainCristóvão Antunes de LannaMarco Antônio M PrettiJéssica Gonçalves Vieira da CruzMarcelo FalchettiMylla M DimasIgor Salerno FilgueirasOtavio Cabral-MarquesRodrigo Nalio RamosFabiane Carvalho de MacedoFabiana Resende RodriguesNina Carrossini BastosJessé Lopes da SilvaEdroaldo Lummertz da RochaCláudia Bessa Pereira ChavesAndreia Cristina de MeloPedro Manoel Mendes de Moraes-VieiraMarcelo Alves da Silva MoriMariana BoroniPublished in: Nature communications (2024)
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.