Table 2.
MDSC-targeted strategies inhibit lung cancer progression
| Refs. | Therapeutic strategy/compound | Targeted process | Tumor model | Implications |
|---|---|---|---|---|
| [98] | P53 vaccine and ATRA | Lin−HLA-DR−CD33+MDSCs depletion | Extensive stage SCLC patients |
1. Enhancement p53-specific immune response 2. Better clinical response |
| [99] | Bevacizumab and EGFR TKI | Reduced the level of circulating S100A9 positive M-MDSCs | Patients with IV lung adenocarcinoma harboring an activating EGFR mutation |
1. Improvement intracranial control rate and intracranial lesion TTP in patients with EGFR-mutant lung adenocarcinoma 2. Increased gene signatures associated with CD8 effector genes, Th1 chemokines, and NK cells. |
| [100] | Cabergoline | Reduced the accumulation of MDSCs | LLC1 murine model |
1. Reduction angiogenesis 2. Inhibition lung cancer growth |
| [101] | Cimetidine | Reduced the accumulation of MDSCs | 3LL murine model |
1. Inhibition of tumor growth 2. Enhancement MDSCs apoptosis |
| [9] | Monoclonal anti-Gr1 or anti-Ly6G Abs | MDSC depletion | 3LL murine model |
1. Increased NK- and CD8+ T cell activity 2.Increased anti-angiogenic but reduced pro-angiog marker expression 3.Reduced 3LL lung metastases 4.Inhibition of tumor growth |
| [9] | BMA-OVA + anti-Gr1 Abs | MDSC depletion | 3LL-OVA murine model |
1. Tumor growth inhibition 2. Increased: splenic production of IFNγ and frequency of IFNγ producing CD4 and CD8 memory (CD44) and activation (CD69) marker expressing T cells |
| [102] | Gemcitabine + SOD mim | MDSC depletion | 3LL murine model |
1. Inhibition tumor growth 2. Enhances the quantity and quality of both effector and memory CD8+T cell responses. 3. Enhanced cytolytic CD8+ T cell response and further decreased Treg cell infiltration. 4. Improved long-term survival of mice bearing lung cancer 5. Thiol-dependent STAT-3 activation is enhanced in memory cells |
| [103] | IDO1 inhibitor | Reduced the percentages of F4/80+Gr1intCD11b+ MDSCs | Anti-PD-1-resistant cell line (344SQ-R) murine model |
1. Inhibition suppresses tumor growth and lung metastases in anti-PD1 resistant tumors 2. Reduction both Kyn levels and Kyn:Trp 3. Reactivation CD8+ T cells 4. Reduction IDO1 expression of F4/80 + Gr1intCD11b + MDSCs and the percentage of IDO1+CD11b+ DCs in anti-PD1 resistant tumors. |
| [104] | Entinostat+ anti-PD-1 antibody | Reduced the immunosuppressive activity of MDSCs | 3LL murine model |
1. Enhanced anti-PD-1 immunotherapy 2. Decrease in the protein levels of FoxP3 in the circulating CD4+FoxP3+cell subtype 3. Increase in the CD8+ T - Treg cells ratio 4. Reduction of tumor infiltrating macrophages 5. Increase in MDSC associated trafficking/accumulation cytokines, anti-tumor chemokines, and cytokines |
| [105] | CCL2 antagonist+ anti-PD-1 antibody | Decreased MDSC recruitment | 3LL murine model |
1. Increased the survival time of tumor-bearing mice 2. Enhanced CD4+ and CD8+ T cell infiltration and activation |
| [106] | MEK Inhibitor (Trametinib) + either anti-PD-1 or anti-PD-L1 mAbs | Attenuation of Ly6Ghigh PMN-MDSCs | p53floxflox;KrasLSL-G12D/+.R0sa26LSL-Luciferase/LSL-Luciferase (PKL) - transgenic lung cancer mouse model |
1. Increased antitumor response and survival outcome 2. Increased of tumor-infiltrating CD8+ and CD4+ T cell 3. Suppressed tumor cell proliferation and lead to apoptosis of tumor cells |
| [107] | Carnosic acid | Decreased function and accumulation of MDSCs | 3LL murine model |
1. Enhanced the anti-growth effects of cisplatin on LLC xenografts and reduced the side effects of cisplatin. 2. Increased antitumor response 3. Enhanced cisplatin-induced tumor proliferation inhibition and apoptosis 4. Promoted CD8+ T cells-mediated antitumor immune response |
| [108] | Resveratrol | Decreased PMN-MDSC accumulation | 3LL murine model |
1. Increased antitumor response and survival outcome 2. Promoted the apoptosis of PMN-MDSCs, impair PMN-MDSCs immunosuppressive capacity 3. Boosted M-MDSCs maturation and differentiation |
| [109] | Curcumin | Decreased MDSC accumulation | 3LL murine model |
1. Increased antitumor response 2. Promoted the maturation and differentiation of MDSCs 3. Inhibited the expression level of Arg-1 and ROS 4. Decreased the level of IL-6 |
ATRA All-trans retinoic acid, MEK mitogen-activated protein kinase/extracellular signal-regulated kinase, TTP time to progress, BMA-OVA the vaccine consisted of bone marrow adherent cells (BMA) that had been pulsed with ovalbumen (OVA) protein, SOD mim superoxide dismutase mimetic