A High-Dimensional Window into the Micro-Environment of Triple Negative Breast Cancer

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.

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

“…higher-grade tumors, did not impact the patients' choice of surgical treatment [5][6][7]. Although TNBC tends to be more aggressive, decision-making for surgery likely rests on more traditional clinicopathological variables and patient preferences in disputative TNBC [6].…”

“…Ductal pathology and gene expression analyses have led to further classification of BC into HER2-enhanced, luminal A and B, basal-like, and claudin-low subtypes [ 1 , 4 ]. The claudin-low subtype is primarily diagnosed in women under 45 years of age and is identified by a high expression of epithelial-to-mesenchymal transition-associated genes, low expression of hormone receptor (HR), and low expression of tight junction markers [ 5 ]. Currently, TNBC diagnosis is based on mammography, immunohistochemistry, and radio-imaging.…”

“…Therefore, there is an urgent need to develop novel therapeutic options. Capecitabine has been used in combination with docetaxel, ixabepilone, doxorubicin cyclophosphamide, and paclitaxel in metastatic TNBC [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Many studies have been performed to determine whether patients with TNBC were more likely to choose mastectomy over lumpectomy [ 7 ].…”

“…Many studies have been performed to determine whether patients with TNBC were more likely to choose mastectomy over lumpectomy [ 7 ]. Results revealed that the TN status, while being associated with younger age and higher-grade tumors, did not impact the patients’ choice of surgical treatment [ 5 , 6 , 7 ]. Although TNBC tends to be more aggressive, decision-making for surgery likely rests on more traditional clinicopathological variables and patient preferences in disputative TNBC [ 6 ].…”

spatialGE: Quantification and visualization of the tumor microenvironment heterogeneity using spatial transcriptomics

“…Spatially-resolved transcriptomic (ST) methods have allowed a better understanding of the tumor microenvironment (TME) at an unprecedented resolution (1). Characterizing heterogeneity within the TME is key to cancer prognosis and development of therapies (2,3).…”