Triple Negative Breast Cancer: Molecular Subtype-Specific Immune Landscapes with Therapeutic Implications

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Triple Negative Breast Cancer (TNBC) presents significant heterogeneity.
• Distinct molecular subtypes of TNBC possess unique biological and clinical characteristics.
• The tumor immune microenvironment (TIME) plays a critical role in cancer progression and treatment response.

Purpose of the Study:

• To systematically review and analyze studies investigating the differences in the TIME across various TNBC molecular subtypes.
• To elucidate how immune cell composition and function vary between TNBC subtypes.
• To identify key factors contributing to TIME heterogeneity in TNBC.

Main Methods:

• Systematic literature review of six relevant studies.
• Classification of TNBC samples into molecular subtypes using gene expression profiling and bioinformatic analyses.
• Characterization of the TIME through immunohistochemistry and cell deconvolution methods.

Main Results:

• Significant heterogeneity in immune cell composition was observed across TNBC subtypes.
• The immunomodulatory (IM) subtype showed robust immune infiltration with adaptive immune cells, high PD-L1 expression, and regulatory T cells (Tregs).
• Luminal androgen receptor (LAR) tumors displayed an immunosuppressive TIME with innate immune cells and low tumor-infiltrating lymphocytes (TILs). Mesenchymal stem-like (MSL) tumors had innate immune cells and M2 tumor-associated macrophages (TAMs). Basal-like (BL) and M subtypes exhibited 'immune-cold' phenotypes with poor immune responses.

Conclusions:

• TNBC molecular subtypes exhibit distinct tumor immune microenvironments, influencing therapeutic strategies.
• Understanding TIME heterogeneity is crucial for developing targeted immunotherapies for specific TNBC subtypes.
• Factors like signaling pathway activation, genomic diversity, and metabolic reprogramming contribute to TIME variations in TNBC.