A High-Dimensional Window into the Micro-Environment of Triple Negative Breast Cancer
1
Department of Tumor Biology and Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
2
Department of Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
3
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
4
Departments of Medical Oncology and Tumor Biology and Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(2), 316; https://doi.org/10.3390/cancers13020316
Submission received: 30 November 2020
/
Revised: 8 January 2021
/
Accepted: 12 January 2021
/
Published: 16 January 2021
(This article belongs to the Special Issue Triple-Negative Breast Cancer: Molecular Characteristics, Treatment Challenges and Solutions)
Simple Summary
Triple negative breast cancer (TNBC) shows a substantial level of genomic, cellular, and phenotypic heterogeneity. While genomic heterogeneity and subclonal diversity are prevalent in this subgroup of tumors, a growing body of evidence indicates that the disease course depends on the interaction between cancer cells and the tumor micro-environment (TME). The TME is not static and can change over time, owing to differences in cell numbers, phenotypes, and spatial relationships. Efforts to further elucidate the TME have been aided by a plethora of new technologies that study tumors in a high-dimensional manner. These high-dimensional technologies enable comprehensive analysis of cell phenotypes at the single cell level or the spatial relationships of tumor and immune cells. In this review, we discuss studies in TNBC that unravel specific spatial patterns of cells in the breast TME and single cell phenotypes.
Abstract
Providing effective personalized immunotherapy for triple negative breast cancer (TNBC) patients requires a detailed understanding of the composition of the tumor microenvironment. Both the tumor cell and non-tumor components of TNBC can exhibit tremendous heterogeneity in individual patients and change over time. Delineating cellular phenotypes and spatial topographies associated with distinct immunological states and the impact of chemotherapy will be necessary to optimally time immunotherapy. The clinical successes in immunotherapy have intensified research on the tumor microenvironment, aided by a plethora of high-dimensional technologies to define cellular phenotypes. These high-dimensional technologies include, but are not limited to, single cell RNA sequencing, spatial transcriptomics, T cell repertoire analyses, advanced flow cytometry, imaging mass cytometry, and their integration. In this review, we discuss the cellular phenotypes and spatial patterns of the lymphoid-, myeloid-, and stromal cells in the TNBC microenvironment and the potential value of mapping these features onto tumor cell genotypes.
Keywords:
single cell; immune profiling; breast cancer; spatial profiling; tumor evolution
