Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 18, 2021
- Source ID
- 10.1038/s41467-021-25240-z
Entities
People
- Amanda L. Rinkenbaugh
- Dean Y Maeda
- Florencia Mcallister
- Helen Piwnica-Worms
- Jiansu Shao
- John A. Zebala
- Mingchu Xu
- Sabrina Jeter-jones
- Vidya C. Sinha
- Xiaomei Zhang
- Xinhui Zhou
- Yuan Qi
Organizations
- Cancer Prevention and Research Institute of Texas
- National Institutes of Health
- Stand Up to Cancer
- United States Department of Defense