Differential Survival and Therapy Benefit of Patients with Breast Cancer Are Characterized by Distinct Epithelial and Immune Cell Microenvironments

Lennart Kester, Danielle Seinstra, Annelot G.J. van Rossum, Claire Vennin, Marlous Hoogstraat, Daphne van der Velden, Mark Opdam, Erik van Werkhoven, Kerstin Hahn, Iris Nederlof, Ester H. Lips, Ingrid A.M. Mandjes, A. Elise van Leeuwen-Stok, Sander Canisius, Harm van Tinteren, Alex L.T. Imholz, Johanneke E.A. Portielje, Monique E.M.M. Bos, Sandra D. Bakker, Emiel J. RutgersHugo M. Horlings, Jelle Wesseling, Emile E. Voest, Lodewyk F.A. Wessels, Marleen Kok, Hendrika M. Oosterkamp, Alexander van Oudenaarden, Sabine C. Linn, Jacco van Rheenen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

2 Citaten (Scopus)

Samenvatting

Purpose: Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to therapeutics. In the human setting, this behavior is mainly correlated with the presence of immune cells. Here, in addition to T cells, B cells, macrophages, and mast cells, we identified the relevance of nonimmune cell types for breast cancer survival and therapy benefit, including fibroblasts, myoepithelial cells, muscle cells, endothelial cells, and seven distinct epithelial cell types. Experimental Design: Using single-cell sequencing data, we generated reference profiles for all these cell types. We used these reference profiles in deconvolution algorithms to optimally detangle the cellular composition of more than 3,500 primary breast tumors of patients that were enrolled in the SCAN-B and MATADOR clinical trials, and for which bulk mRNA sequencing data were available. Results: This large data set enables us to identify and subsequently validate the cellular composition of microenvironments that distinguish differential survival and treatment benefit for different treatment regimens in patients with primary breast cancer. In addition to immune cells, we have identified that survival and therapy benefit are characterized by various contributions of distinct epithelial cell types. Conclusions: From our study, we conclude that differential survival and therapy benefit of patients with breast cancer are characterized by distinct microenvironments that include specific populations of immune and epithelial cells.

Originele taal-2Engels
Pagina's (van-tot)960-971
Aantal pagina's12
TijdschriftClinical Cancer Research
Volume28
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 1 mrt. 2022
Extern gepubliceerdJa

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