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Table 2 MDSC-targeted strategies inhibit lung cancer progression

From: Myeloid-derived suppressor cells—new and exciting players in lung cancer

Refs.Therapeutic strategy/compoundTargeted processTumor modelImplications
[98]P53 vaccine and ATRALinHLA-DRCD33+MDSCs depletionExtensive stage SCLC patients1. Enhancement p53-specific immune response
2. Better clinical response
[99]Bevacizumab and EGFR TKIReduced the level of circulating S100A9 positive M-MDSCsPatients with IV lung adenocarcinoma harboring an activating EGFR mutation1. 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]CabergolineReduced the accumulation of MDSCsLLC1 murine model1. Reduction angiogenesis
2. Inhibition lung cancer growth
[101]CimetidineReduced the accumulation of MDSCs3LL murine model1. Inhibition of tumor growth
2. Enhancement MDSCs apoptosis
[9]Monoclonal anti-Gr1 or anti-Ly6G AbsMDSC depletion3LL murine model1. 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 AbsMDSC depletion3LL-OVA murine model1. 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 mimMDSC depletion3LL murine model1. 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 inhibitorReduced the percentages of F4/80+Gr1intCD11b+ MDSCsAnti-PD-1-resistant cell line (344SQ-R) murine model1. 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 antibodyReduced the immunosuppressive activity of MDSCs3LL murine model1. 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 antibodyDecreased MDSC recruitment3LL murine model1. 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 mAbsAttenuation of Ly6Ghigh PMN-MDSCsp53floxflox;KrasLSL-G12D/+.R0sa26LSL-Luciferase/LSL-Luciferase (PKL) - transgenic lung cancer mouse model1. 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 acidDecreased function and accumulation of MDSCs3LL murine model1. 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]ResveratrolDecreased PMN-MDSC accumulation3LL murine model1. 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]CurcuminDecreased MDSC accumulation3LL murine model1. 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
  1. 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