RESUMEN

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.

Asunto(s)

Glicoproteínas de Membrana , Células Mieloides , Neoplasias , Receptores Inmunológicos , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Análisis de la Célula Individual/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Células Mieloides/metabolismo , Células Mieloides/patología , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Pronóstico , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Femenino , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética