Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer

Kajiwara, Yoshinori; Tazawa, Hiroshi; Yamada, Motohiko; Kanaya, Nobuhiko; Fushimi, Takuro; Kikuchi, Shinichi; Kuroda, Shigetoshi; Ohara, Toshiaki; Noma, Kazuhiro; Yoshida, Ryuichi; Umeda, Yuzo; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi

doi:10.1007/s00262-022-03334-x

Cited by 16 publications

(8 citation statements)

References 54 publications

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“…The inhibition of the growth factors and recruiting factors derived from tumor cells or the TME can inhibit the population of MDSCs in PDAC and their functions. For example, gemcitabine (GEM)-resistant PDAC cells can express higher levels of PD-L1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to parental PDAC cells, which can cause the accumulation of MDSCs and an immunosuppressive TME [105]. In cell and animal tumor models, a combination therapy with p53-expressing telomerase-specific oncolytic adenovirus OBP-702 and PD-L1 blockade or PD-1 blockade can improve the antitumor efficacy of PD-L1/PD-1 blockade and inhibit the GM-CSF-induced accumulation of MDSCs and immunosuppressive TME [105,106].…”

Section: Myeloid-derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

“…For example, gemcitabine (GEM)-resistant PDAC cells can express higher levels of PD-L1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to parental PDAC cells, which can cause the accumulation of MDSCs and an immunosuppressive TME [105]. In cell and animal tumor models, a combination therapy with p53-expressing telomerase-specific oncolytic adenovirus OBP-702 and PD-L1 blockade or PD-1 blockade can improve the antitumor efficacy of PD-L1/PD-1 blockade and inhibit the GM-CSF-induced accumulation of MDSCs and immunosuppressive TME [105,106]. Chemokines/chemokine receptors such as CXCL2/CXCR2 and CCL2/CCR2 facilitate the recruitment of myeloid neutrophils and macrophages to PDAC to induce an immunosuppressive TME [107].…”

Section: Myeloid-derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

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Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Olaoba,

Yang,

Adelusi

et al. 2024

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a very poor prognosis. Despite advancements in treatment strategies, PDAC remains recalcitrant to therapies because patients are often diagnosed at an advanced stage. The advanced stage of PDAC is characterized by metastasis, which typically renders it unresectable by surgery or untreatable by chemotherapy. The tumor microenvironment (TME) of PDAC comprises highly proliferative myofibroblast-like cells and hosts the intense deposition of a extracellular matrix component that forms dense fibrous connective tissue, a process called the desmoplastic reaction. In desmoplastic TMEs, the incessant aberration of signaling pathways contributes to immunosuppression by suppressing antitumor immunity. This feature offers a protective barrier that impedes the targeted delivery of drugs. In addition, the efficacy of immunotherapy is compromised because of the immune cold TME of PDAC. Targeted therapy approaches towards stromal and immunosuppressive TMEs are challenging. In this review, we discuss cellular and non-cellular TME components that contain actionable targets for drug development. We also highlight findings from preclinical studies and provide updates about the efficacies of new investigational drugs in clinical trials.

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Section: Myeloid-derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

Section: Myeloid-derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Olaoba,

Yang,

Adelusi

et al. 2024

Cancers

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“…This approach facilitates the removal of cancer cells and the formation of immune memory. In a preclinical study, high levels of expression of GM-CSF was found to stimulate durable antitumor activity with vaccine-based therapy ( 104 ). The GVAX vaccine was therefore developed for treating pancreatic cancer.…”

Section: Cancer Vaccinesmentioning

confidence: 99%

Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application

Zheng,

Liu,

Zhang

et al. 2024

Front. Immunol.

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Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

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“…These viruses can be utilized to inhibit the production of GM-CSF. When combined with PD-L1 blockers, they can effectively impede the growth of gemcitabine-resistant PDAC [34]. MDSCs can enhance EMT by modulating the CCL2-CCR4 axis and promote tissue fibrosis through the CCL5-CCR5 axis [35].…”

Section: Mdscsmentioning

confidence: 99%

Current Status and Perspectives of Pancreatic Cancer Tumor Microenvironment and Therapy

2024

IJFM

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Pancreatic ductal adenocarcinoma (PDAC) is commonly known as the "king of cancers" because of its exceptionally aggressive nature and poor prognosis for patients. Moreover, the pancreas, being a retroperitoneal organ, presents a lack of specific markers, making early identification difficult. The tumor microenvironment (TME) consists of tumor cells, stromal cells, immune cells and cytokines, etc. together. Antitumor medications cannot penetrate PDAC due to its high mesenchymal component content, which also restricts immune cells to infiltrate the tumor tissue. At the same time, the TME of PDAC lacks anti-tumor immune cell infiltration and has strong immunosuppressive properties, and the components of TME play an important role in tumor growth, angiogenesis, immunosuppression, and resistance to chemotherapy and targeted drugs. In this paper, we provide an overview of the composition, biological properties and research progress of immunotherapy of TME in PDAC, in the hope of bringing new ideas for the treatment of PDAC.

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Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer

Cited by 16 publications

References 54 publications

Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application

Current Status and Perspectives of Pancreatic Cancer Tumor Microenvironment and Therapy

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