Table 2 MDSC-targeted strategies inhibit lung cancer progression

[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⁺Gr1^intCD11b⁺ 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

p53^floxflox;Kras^LSL-G12D/+.R_0sa26^{LSL-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