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- Title
Triple Negative Breast Cancer: Molecular Subtype-Specific Immune Landscapes with Therapeutic Implications.
- Authors
Syrnioti, Antonia; Petousis, Stamatios; Newman, Lisa A.; Margioula-Siarkou, Chrysoula; Papamitsou, Theodora; Dinas, Konstantinos; Koletsa, Triantafyllia
- Abstract
Simple Summary: Triple Negative Breast Cancer (TNBC) comprises approximately 15–20% of all breast cancer (BC) cases, is often diagnosed at an advanced stage, and is generally associated with an adverse clinical outcome. This systematic review explores differences in the tumor immune microenvironment (TIME) across various molecular subtypes of TNBC. Six studies meeting our inclusion criteria were analyzed, revealing diverse TIMEs with distinct compositions among TNBC molecular subtypes. The IM subtype shows robust immune infiltration, while LAR and MSL subtypes display more immunosuppressive milieu. The spatial distribution of immune cells and immune checkpoint expression varies across TNBC molecular subtypes. TIME heterogeneity reflects genomic diversity, along with differential signaling pathways and metabolic activation. Understanding TIME variability offers strategic opportunities for personalized therapeutic interventions in TNBC. Triple Negative Breast Cancer (TNBC) is characterized by distinct molecular subtypes with unique biological and clinical features. This systematic review aimed to identify articles examining the differences in the tumor immune microenvironment (TIME) across different TNBC molecular subtypes. Six studies meeting inclusion criteria were analyzed, utilizing gene expression profiling and bioinformatic analyses to classify TNBC samples into molecular subtypes, as well as immunohistochemistry and cell deconvolution methods to characterize the TIME. Results revealed significant heterogeneity in immune cell composition among TNBC subtypes, with the immunomodulatory (IM) subtype demonstrating robust immune infiltration, composed mainly of adaptive immune cells along with an increased density of CTLA-4+ and PD-1+ TILs, high PD-L1 tumor cell expression, and upregulation of FOXP3+ Tregs. A more immunosuppressive TIME with a predominance of innate immune cells and lower levels of tumor-infiltrating lymphocytes (TILs) was observed in luminal androgen receptor (LAR) tumors. In mesenchymal stem-like (MSL) tumors, the TIME was mainly composed of innate immune cells, with a high number of M2 tumor-associated macrophages (TAMs), while the BL and M tumors displayed poor adaptive and innate immune responses, indicating an "immune-cold" phenotype. Differential activation of signaling pathways, genomic diversity, and metabolic reprogramming were identified as contributors to TIME heterogeneity. Understanding this interplay is crucial for tailoring therapeutic strategies, especially regarding immunotherapy.
- Subjects
BREAST tumors; IMMUNOTHERAPY; SYMPTOMS; IMMUNE checkpoint inhibitors; GENE expression; SYSTEMATIC reviews; MEDLINE; BIOINFORMATICS; IMMUNOHISTOCHEMISTRY; MEDICAL databases; GENE expression profiling; ONLINE information services
- Publication
Cancers, 2024, Vol 16, Issue 11, p2094
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16112094