Overview of some important immune cell types, their roles in the TME of BC, associated markers, and therapeutic implications
| Immune cell type | Role in BC TME | Markers | Therapeutic implications |
|---|---|---|---|
| Tumor-associated macrophages (TAMs) | TAMs are abundant in the TME and polarize into pro-tumorigenic M2 macrophages, promoting immunosuppression, angiogenesis, and tumor progression. | CD68, CD163 (M2), iNOS (M1), ARG1 | Reprogramming TAMs from M2 to M1 using cytokines or inhibitors can enhance anti-tumor immunity. Targeting PD-L1 on TAMs or disrupting recruitment pathways (e.g., CCL2-CCR2) is under investigation |
| Myeloid-derived suppressor cells (MDSCs) | MDSCs suppress T cell activation, inhibit immune responses, and create a microenvironment favoring tumor progression. | CD11b, CD33, CD15, CD14 | Targeting MDSCs with agents that inhibit recruitment or function can improve immune checkpoint blockade efficacy |
| Regulatory T cells (Tregs) | Tregs suppress immune responses by inhibiting cytotoxic T cells and natural killer cells, contributing to immune escape. | CD4, CD25, FOXP3, TIGIT | Reducing Treg activity or targeting TIGIT can enhance anti-tumor immunity |
| Cytotoxic T lymphocytes (CTLs) | CTLs mediate anti-tumor effects by recognizing and killing tumor cells. In BC, their activity is often impaired due to TME immunosuppression. | CD8, granzyme B, perforin | Immune checkpoint inhibitors targeting PD-1/PD-L1 restore CTL functionality and enhance tumor cell killing |
| Natural killer (NK) cells | NK cells can kill tumor cells directly and influence the TME through cytokine production. | CD56, CD16, NKp46 | Activating NK cells or enhancing their cytotoxicity through cytokines or immune modulators can improve anti-tumor responses |
| Dendritic cells (DCs) | DCs are crucial for antigen presentation and the activation of T cells. However, in the TME, their functionality is often impaired. | CD11c, HLA-DR, CD80/CD86 | Therapies to enhance DC activation or antigen presentation are being explored, including DC-based vaccines |
| B cells | B cells exhibit dual roles, promoting or inhibiting tumor progression depending on subtype. They are involved in antibody production and modulating immune responses. | CD19, CD20, CD138, CXCL13 | Targeting immunosuppressive regulatory B cells (Bregs) or enhancing tertiary lymphoid structures (TLSs) can improve anti-tumor immunity |
| Cancer stem cells (CSCs) | CSCs contribute to tumor recurrence, therapy resistance, and immune evasion by interacting with the TME. | CD44, CD133, OCT4, SOX2 | Targeting CSCs with therapies directed at their unique markers and pathways (e.g., Wnt/β-catenin, STAT3) may reduce recurrence and enhance treatment efficacy |
| Cancer-associated fibroblasts (CAFs) | CAFs remodel the extracellular matrix, promote immune evasion, and secrete cytokines that suppress T cell activity. | α-SMA, FAP, PDGFRα/β, CXCL12 | Modulating CAF activity or targeting pathways like TGF-β signaling can enhance immune cell infiltration and therapy responsiveness |
| Neutrophils | Neutrophils release enzymes that remodel the extracellular matrix and promote angiogenesis and metastasis. | CD66b, MPO, CXCR1/CXCR2 | Targeting tumor-associated neutrophils (TANs) or their recruitment pathways (e.g., CXCR1/2) may reduce metastasis and enhance anti-tumor responses |
TME: tumor microenvironment; iNOS: inducible nitric oxide synthase; PD-L1: programmed death-ligand 1; BC: bladder cancer; PD-1: programmed cell death protein-1; SOX2: SRY homology box 2; FAP: fibronectin attachment protein; TGF-β: transforming growth factor-beta