Table 1.
Summary of studies investigating TIME in relation to TNBC molecular subtypes.
| Study (Year) | TNBC Molecular Subtypes | TIME Cellular Evaluation | IC Investigation | Main Results |
|---|---|---|---|---|
| Bareche et al. 2020 [22] | Lehmann’s (BL1 and BL2, IM, LAR, M, MSL) Jiang’s-FUSCC (BLIS, IM, LAR, MES) Burstein’s (BLIS, BLIA, LAR, MES) |
aDCs, iDCs, B cells, NK cells, CD4+ helper (Th1 and Th2), CD8+ T cells, Tcm, Tem, Tfh, γδ T cells, and Tregs, neutrophils, eosinophils, mast cells, macrophages | no | IM subtype: enriched with adaptive immune cells. MSL subtype: enriched with innate immune cells. LAR subtype: enriched with innate immune cells (to a lesser extent than MSL). BL and M subtype: poor adaptive and innate immune responses. |
| Kim et al. 2020 [23] | MSL, LAR, IM, SL | DCs, B cells, NK cells, CD4+ T cells, Tregs, CD8+ T cells, γδ T cells, plasma cells, neutrophils, eosinophils, mast cells, macrophages | PD-L1, CTLA-4 expression | IM subtype: strongly immune-infiltrated, particularly adaptive immune cells and activated NK cells. MSL subtype: high incidence of M2 macrophages. PD-L1, and CTLA4 significantly enhanced in the IM subtype tumors. |
| Zhang et al. 2020 [24] | BL1, BL2, IM, M, MSL, and LAR | DCs, Th1 cells, Th2 cells, Tregs, neutrophils, macrophages | PD-L1, PD-1, CTLA-4 gene expression | Identification of 8 immune-related hub-genes as prognostic indicators, characterized “immune-hot” status in the TNBC IM subtype. PD-L1, PD-1, and CTLA-4 genes more enriched in the IM subtype. |
| Rodríguez-Bautista et al. 2021 [25] | IM vs. non-IM | CD4+ T cells, CD8+ T cells, Tregs | PD-1, PD-L1, CTLA-4 IHC | IM subtype: enriched with CD8+ TILs and FOXP3+ T-cells. PD-1+ TILs, CTLA-4+ TILs, and PD-L1+ tumor cells increased in the IM subtype. |
| Thompson et al. 2022 [26] |
LAR vs. non-LAR | B cells, NK cells, T cells, CD4+ T cells, CD8+ T cells, plasma cells | no | LAR subtype: lower levels of TILs, increased CD4+ and CD8+ cells, and decreased cycling and regulatory T cells, compared to non-LAR. Non-LAR responders to NAC: increased NK cells, Th cells, cycling T-cells, plasma cells, compared to the non-LAR non-responders. |
| Suntiparpluacha et al. 2023 [27] | Four subgroups, three of which corresponded to Lehmann’s LAR, BL2, and M subtypes | B cells, CD8+ T cells, neutrophils, MDSCs |
PD-L1, PD-1 gene expression |
Group 1 (corresponding to LAR subtype): lower amount of CD8+ T cells, MDSCs, B cells, and neutrophils. Group 2 (corresponding to BL2 subtype): enriched with CD8+ T cells and high PD-L1 and PD-1 gene expression. Group 3 (corresponding to M subtype): increased neutrophils. |
Abbreviations TIME: tumor immune microenvironment; TNBC: triple negative breast cancer; IHC: immunohistochemistry; IC: immune checkpoint; FUSCC: Fudan University Shanghai Cancer Center; BL: basal-like; IM: immunomodulatory; LAR: luminal androgen receptor; M: mesenchymal; MSL: mesenchymal stem-like; BLIS: basal-like immune-suppressed; BLIA: basal-like immune activated; SL: stem-like; aDCs: activated dendritic cells; iDCs: inactivated dendritic cells; NK: natural killer; Th: T helper cells; Tregs: T regulatory cells; Tfh: follicular helper T cells; γδ: gamma delta T cells, PD-1: programmed cell death; PD-L1: programmed cell death ligand; CTLA-4: cytotoxic T-lymphocyte associated protein 4; MDSCs: myeloid-derived suppressor cells; NAC: neoadjuvant chemotherapy.