Single-cell and spatial mapping reveals GCLC+ mesenchymal tumor cells linked with favorable outcomes in TNBC
Abstract
Oxidative stress response (OSR) is suggested as a therapeutic target in triple negative breast cancer (TNBC). However, the cell type specificity and spatial distribution of OSR genes and proteins remain poorly defined. We re-analyzed public datasets, demostrating high OSR gene expression in TNBC tumor cells. We generated a multiplex immunofluorescence dataset of 345 TNBC samples that showed OSR proteins GCLC and NQO1 are differentially expressed across tumor, immune, and stromal cells, and elevated in inflamed regions. We identified a mesenchymal-like tumor cell state characterized by co-expression of GCLC and vimentin (GCLC⁺VIM⁺), with increased proliferation and reduced anastasis-associated signatures, suggesting a vulnerability to chemotherapy. Consistently, TNBC cell lines with higher GCLC expression showed increased sensitivity to cisplatin. Moreover, patients with higher proportions of GCLC⁺VIM⁺ tumor cells had longer overall survival. Our findings indicate that OSR proteins are expressed in spatially and phenotypically distinct tumor microenvironments, and that the GCLC⁺VIM⁺ tumor cell state is associated with favorable outcomes in TNBC.
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BibTeX
@article{girnius2026singlecell,
title = {{Single-cell and spatial mapping reveals GCLC+ mesenchymal tumor cells linked with favorable outcomes in TNBC}},
author = {Nomeda Girnius and Tuulia Vallius and Wenqing Chen and Inga-Maria Launonen and Sara Palomino-Echeverria and Jia-Ren Lin and Caitlin E. Mills and Silja Kauppila and Pauliina Kronqvist and Antti Ellonen and Merja Perala and Eloise Withnell and Yu-An Chen and Maria Secrier and Sandro Santagata and Peter K. Sorger and Anniina Färkkilä},
journal = {Communications Biology},
year = {2026},
month = oct,
doi = {10.1038/s42003-026-11175-y},
url = {https://www.nature.com/articles/s42003-026-11175-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell and spatial mapping reveals GCLC+ mesenchymal tumor cells linked with favorable outcomes in TNBC
AU - Nomeda Girnius
AU - Tuulia Vallius
AU - Wenqing Chen
AU - Inga-Maria Launonen
AU - Sara Palomino-Echeverria
AU - Jia-Ren Lin
AU - Caitlin E. Mills
AU - Silja Kauppila
AU - Pauliina Kronqvist
AU - Antti Ellonen
AU - Merja Perala
AU - Eloise Withnell
AU - Yu-An Chen
AU - Maria Secrier
AU - Sandro Santagata
AU - Peter K. Sorger
AU - Anniina Färkkilä
PY - 2026
DA - 2026/10/23
JO - Communications Biology
DO - 10.1038/s42003-026-11175-y
UR - https://www.nature.com/articles/s42003-026-11175-y
AB - Oxidative stress response (OSR) is suggested as a therapeutic target in triple negative breast cancer (TNBC). However, the cell type specificity and spatial distribution of OSR genes and proteins remain poorly defined. We re-analyzed public datasets, demostrating high OSR gene expression in TNBC tumor cells. We generated a multiplex immunofluorescence dataset of 345 TNBC samples that showed OSR proteins GCLC and NQO1 are differentially expressed across tumor, immune, and stromal cells, and elevated in inflamed regions. We identified a mesenchymal-like tumor cell state characterized by co-expression of GCLC and vimentin (GCLC⁺VIM⁺), with increased proliferation and reduced anastasis-associated signatures, suggesting a vulnerability to chemotherapy. Consistently, TNBC cell lines with higher GCLC expression showed increased sensitivity to cisplatin. Moreover, patients with higher proportions of GCLC⁺VIM⁺ tumor cells had longer overall survival. Our findings indicate that OSR proteins are expressed in spatially and phenotypically distinct tumor microenvironments, and that the GCLC⁺VIM⁺ tumor cell state is associated with favorable outcomes in TNBC.
SN - 2399-3642
ER -