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

Vidya C. Sinha, Amanda L. Rinkenbaugh, Mingchu Xu, Xinhui Zhou, Xiaomei Zhang, Sabrina Jeter-Jones, Jiansu Shao, Yuan Qi, John A. Zebala, Dean Y. Maeda, Florencia McAllister and Helen Piwnica-Worms ()
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Vidya C. Sinha: The University of Texas MD Anderson Cancer Center
Amanda L. Rinkenbaugh: The University of Texas MD Anderson Cancer Center
Mingchu Xu: The University of Texas MD Anderson Cancer Center
Xinhui Zhou: The University of Texas MD Anderson Cancer Center
Xiaomei Zhang: The University of Texas MD Anderson Cancer Center
Sabrina Jeter-Jones: The University of Texas MD Anderson Cancer Center
Jiansu Shao: The University of Texas MD Anderson Cancer Center
Yuan Qi: The University of Texas MD Anderson Cancer Center
John A. Zebala: Syntrix Pharmaceuticals, Inc.
Dean Y. Maeda: Syntrix Pharmaceuticals, Inc.
Florencia McAllister: The University of Texas MD Anderson Cancer Center
Helen Piwnica-Worms: The University of Texas MD Anderson Cancer Center

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25240-z

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