Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast.

Autor: Sinha VC; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Rinkenbaugh AL; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Xu M; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Zhou X; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Zhang X; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Jeter-Jones S; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Shao J; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Qi Y; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Zebala JA; Syntrix Pharmaceuticals, Inc., Auburn, WA, 98001, USA., Maeda DY; Syntrix Pharmaceuticals, Inc., Auburn, WA, 98001, USA., McAllister F; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Piwnica-Worms H; Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. hpiwnica-worms@mdanderson.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Aug 18; Vol. 12 (1), pp. 5024. Date of Electronic Publication: 2021 Aug 18.
DOI: 10.1038/s41467-021-25240-z
Abstrakt: There is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz: