ABSTRACT
Introduction
In contrast to other breast cancer subtypes, there are currently limited options of targeted therapies for triple-negative breast cancer (TNBC). Immense research has demonstrated that not only cancer cells but also stromal cells and immune cells in the tumor microenvironment (TME) play significant roles in the progression of TNBC. It is thus critical to understand the components of the TME of TNBC and the interactions between the various cell populations.
Areas covered
The components of the TME of TNBC identified by single-cell technologies are reviewed. Furthermore, the molecular interactions between the cells and the potential therapeutic targets contributing to the progression of TNBC are discussed.
Expert opinion
Single-cell omics studies have contributed to the classification of cells in the TME and the identification of important cell types involved in the progression and the treatment of the tumor. The interactions between cancer cells and stromal cells/immune cells in the TME have led to the discovery of potential therapeutic targets. Experimental data with spatial and temporal resolution will further boost the understanding of the TME of TNBC.
Article highlights
Specific subpopulations of T cells have been shown to associate with better prognosis. Furthermore, scRNA-seq studies of TNBC patients identified T cell subpopulations that expand during immunotherapy. Although T cells have been the main target of study, several studies show that B cells play a critical role in the immune response against TNBC cells. The activity of NK cells in TNBC has been shown to be mostly suppressed.
TAMs are the major component of the myeloid cells in TNBC. TAMs show a spectrum of phenotypes and are generally associated with poor prognosis. Monocytes and MDSCs are generally thought to promote the progression of TNBC. However, the heterogeneity within monocytes and MDSCs, along with the role of minor subpopulations on TNBC progression, remain unclear. Type 1 conventional dendritic cells are associated with better prognosis, while monocyte-derived dendritic cells are associated with poor prognosis. Contradicting studies have been reported for the role of plasmacytoid dendritic cells on TNBC progression.
Myofibroblast-like and inflammatory CAFs are the two major populations of CAFs in TNBC. The presence of antigen presenting CAFs in TNBC is debatable. Certain subpopulations of CAFs are associated with immunosuppression.
There is not much single-cell omics data about endothelial cells in TNBC. Crosstalk between endothelial cells and TNBC cells affects the migratory activity of cancer cells and endothelial cells, which may contribute to invasion and metastasis.
Acknowledgments
The authors thank members of the Popel laboratory Adam Mirando, Niranjan Pandey, Akash Patil, Hanwen Wang, and Theinmozhi Arulraj for reading the manuscript and critical comments.
Declaration of interests
V Stearns: Research funding to institution: AbbVie, Biocept, Novartis, Pfizer, Puma Biotechnology, QUE Oncology. Advisory board: Novartis 10/25/2021. Chair, Data and Safety Monitoring Board: AstraZeneca. Non-financial support: Foundation Medicine Study Assays.
CA Santa-Maria: Research funding to institution: Pfizer, AstraZeneca, Merck, BMS, Genentech, Tesaro (GSK). Ad board (no honoraria): BMS, Pfizer, Merck. Ad board (honoraria accepted): Seattle Genetics, Genomic Health, Athenex.
AS Popel: Research funding to institution: AstraZeneca, Boehringer Ingelheim, CytomX Therapeutics. Founder and Chief Scientific Advisor: AsclepiX Therapeutics. Consulting: AsclepiX Therapeutics, CytomX Therapeutics.
N Furukawa declares no competing interests. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict-of-interest policies.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.