Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells

Otsuka, Kenji; Mitsuhashi, Atsushi; Goto, Hisatsugu; Hashimoto, Masaki; Koyama, Kazuya; Ogawa, Hirohisa; Ogino, Hirokazu; Saijo, Atsuro; Kozai, Hiroyuki; Yoneda, Hiroto; Tobiume, Makoto; Kishuku, Masatoshi; Ishizawa, Keisuke; Nishioka, Yasuhiko

doi:10.1016/j.lungcan.2020.05.023

Cited by 15 publications

(15 citation statements)

References 49 publications

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“…We next examined whether tumor cells are the main source of CXCL10/11 in response to ICI therapy. In our previous reports, PD‐1 blockade induced IFN‐γ expression in TILs in AB1‐HA tumor‐bearing mice 30 . In the present study, we also showed that IFN‐γ was specifically expressed in CD4 + or CD8 + TILs in AB1‐HA tumor‐bearing mice treated with PD‐L1 blockade (Figure ).…”

Section: Resultssupporting

confidence: 83%

“…In our previous reports, PD‐1 blockade induced IFN‐γ expression in TILs in AB1‐HA tumor‐bearing mice. 30 In the present study, we also showed that IFN‐γ was specifically expressed in CD4 + or CD8 + TILs in AB1‐HA tumor‐bearing mice treated with PD‐L1 blockade (Figure S6 ). Thus, as we observed that PD‐L1 blockade did not affect tumor angiogenesis in BALB/c nude mice, there was a possibility that the expression of angiostatic chemokines would be induced by T cell‐derived IFN‐γ.…”

Section: Resultssupporting

confidence: 71%

“…In addition, treatment with anti‐PD‐L1 Ab induced the upregulation of the IFNG gene in both ICI‐sensitive and ICI‐resistant cell lines, whereas CXCL10/11 were induced only in ICI‐responder cells (Figure 6). Tumor‐infiltrating lymphocytes are recognized as the main source of IFN‐γ in the tumor microenvironment 30 . The present findings suggest that T cell‐derived IFN‐γ was essential for the upregulation of the CXCL10/11 expression in tumor tissue treated with ICIs.…”

Section: Discussionmentioning

confidence: 49%

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Programmed death (PD)‐1/PD‐ligand 1 blockade mediates antiangiogenic effects by tumor‐derived CXCL10/11 as a potential predictive biomarker

et al. 2021

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Immune checkpoint inhibitor (ICI) programmed death (PD)‐1/PD‐ligand 1 (PD‐L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti‐PD‐L1/PD‐1 Ab in tumor angiogenesis. In syngeneic mouse models, anti‐PD‐L1 Ab inhibited tumor angiogenesis and induces net‐like hypoxia only in ICI‐sensitive cell lines. In tumor tissue and serum of ICI‐sensitive cell line‐bearing mice, interferon‐γ (IFN‐γ) inducible angiostatic chemokines CXCL10/11 were upregulated by PD‐L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN‐γ stimulation in tumor cell lines correlated with the sensitivity of PD‐L1 blockade. The CXCL10/11 receptor CXCR3‐neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD‐L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti‐PD‐1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD‐1/PD‐L1 blockade and identify tumor‐derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity.

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Section: Resultssupporting

confidence: 83%

Section: Resultssupporting

confidence: 71%

Section: Discussionmentioning

confidence: 49%

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Programmed death (PD)‐1/PD‐ligand 1 blockade mediates antiangiogenic effects by tumor‐derived CXCL10/11 as a potential predictive biomarker

et al. 2021

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“…In one murine study, Gr1 + MDSC-like infiltration of AB1-HA tumors was significantly reduced by cisplatin-pemetrexed, and Gr1 + depletion alongside PD-1 blockade resulted in slower tumor growth. 81 Systemic depletion of MDSCs has also been noted. 53 82 In humans, gemcitabine treatment can depress CD11b + /CD33 + /HLA-DR − MDSC numbers in PBMCs, associated with increased T-cell proliferation.…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy

Harber

Kamata

Pritchard

et al. 2021

J Immunother Cancer

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Malignant pleural mesothelioma (MPM) is an incurable cancer with a dismal prognosis and few effective treatment options. Nonetheless, recent positive phase III trial results for immune checkpoint blockade (ICB) in MPM herald a new dawn in the fight to advance effective treatments for this cancer. Tumor mutation burden (TMB) has been widely reported to predict ICB in other cancers, but MPM is considered a low-TMB tumor. Similarly, tumor programmed death-ligand 1 (PD-L1) expression has not been proven predictive in phase III clinical trials in MPM. Consequently, the precise mechanisms that determine response to immunotherapy in this cancer remain unknown. The present review therefore aimed to synthesize our current understanding of the tumor immune microenvironment in MPM and reflects on how specific cellular features might impact immunotherapy responses or lead to resistance. This approach will inform stratified approaches to therapy and advance immunotherapy combinations in MPM to improve clinical outcomes further.

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“…Combinative use of cisplatin, anti-PD-1 antibody, and pemetrexed was found to enhance the antitumor immune responses in mesothelioma mice at least in part due to the decrease of MDSC infiltration. 154 Another study indicated that in HPV-related cancers, cisplatin was able to sustain an induction of tumor-specific CD8 + T cells along with a decrease of CD11b + GR-1 int myeloid cells, and a combination with anti-CTLA4 helped improve the efficacy. 155 As discussed above, chemotherapy could induce ICD, which partly explained the enhanced efficacy of combinative administration of chemotherapy and immunotherapy.…”

Section: Targeting Mdsc: New Therapeutic Strategies and Insights For Icb Anti-cancer Therapymentioning

confidence: 99%

Targeting MDSC for Immune-Checkpoint Blockade in Cancer Immunotherapy: Current Progress and New Prospects

Liu

Zhu

et al. 2021

Clin Med Insights Oncol

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Immune-checkpoint blockade (ICB) demonstrated inspiring effect and great promise in anti-cancer therapy. However, many obstacles, such as drug resistance and difficulty in patient selection, limited the efficacy of ICB therapy and awaited to be overcome. By timely identification and intervention of the key immune-suppressive promotors in the tumor microenvironment (TME), we may better understand the mechanisms of cancer immune-escape and use novel strategies to enhance the therapeutic effect of ICB. Myeloid-derived suppressor cell (MDSC) is recognized as a major immune suppressor in the TME. In this review, we summarized the roles MDSC played in the cancer context, focusing on its negative biologic functions in ICB therapy, discussed the strategies targeted on MDSC to optimize the diagnosis and therapy process of ICB and improve the efficacy of ICB therapy against malignancies.

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Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells

Cited by 15 publications

References 49 publications

Programmed death (PD)‐1/PD‐ligand 1 blockade mediates antiangiogenic effects by tumor‐derived CXCL10/11 as a potential predictive biomarker

Programmed death (PD)‐1/PD‐ligand 1 blockade mediates antiangiogenic effects by tumor‐derived CXCL10/11 as a potential predictive biomarker

Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy

Targeting MDSC for Immune-Checkpoint Blockade in Cancer Immunotherapy: Current Progress and New Prospects

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