mTOR Inhibitors Can Enhance the Anti-Tumor Effects of DNA Vaccines through Modulating Dendritic Cell Function in the Tumor Microenvironment

Chen, Yuli; Lin, Han‐Wei; Sun, Nai-Yun; Yie, Jr-Chi; Hung, Hsueh-Chih; Chen, Chi-An; Sun, Wei‐Zen; Cheng, Wen‐Fang

doi:10.3390/cancers11050617

Cited by 14 publications

(12 citation statements)

References 39 publications

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“…In addition to NK cells, DC is also believed to be related to the mTOR signaling pathway in recent years. Chen et al [33] concluded that apoptosis of DC-derived from bone marrow mononuclear (BMM) cells was reduced after treatment with mTOR inhibitors. They also found that BMM cellderived DCs had better antigen presentation capabilities and that e7-specific cytotoxic CD8+ T lymphocytes activated by these DCs had greater anti-tumor activity.…”

Section: Natural Killer Cells and Dendritic Cellsmentioning

confidence: 99%

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

et al. 2020

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Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases. The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism. Therefore, the mTOR signaling pathway is a hot target in anti-tumor therapy research. In recent years, a variety of newly discovered mTOR inhibitors have entered clinical studies, and a variety of drugs have been proven to have high activity in combination with mTOR inhibitors. The purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduce the research progress of mTOR inhibitors in the tumor field.

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Section: Natural Killer Cells and Dendritic Cellsmentioning

confidence: 99%

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

et al. 2020

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“…Using microparticles encapsulating rapamycin, the low dose release of rapamycin polarized vaccine-induced T cells toward central memory phenotypes, which could enhance anti-tumor immunotherapy [354]. Rapalogs could also modulate dendritic cell function thus enhancing anti-tumor effects of DNA vaccines [355,356]. A better understanding of the metabolic dependencies of various immune cells should provide more opportunities for immunotherapy.…”

Section: Immunotherapymentioning

confidence: 99%

Targeting mTOR and Metabolism in Cancer: Lessons and Innovations

Magaway

Kim

Jacinto

2019

Cells

172

128

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Cancer cells support their growth and proliferation by reprogramming their metabolism in order to gain access to nutrients. Despite the heterogeneity in genetic mutations that lead to tumorigenesis, a common alteration in tumors occurs in pathways that upregulate nutrient acquisition. A central signaling pathway that controls metabolic processes is the mTOR pathway. The elucidation of the regulation and functions of mTOR can be traced to the discovery of the natural compound, rapamycin. Studies using rapamycin have unraveled the role of mTOR in the control of cell growth and metabolism. By sensing the intracellular nutrient status, mTOR orchestrates metabolic reprogramming by controlling nutrient uptake and flux through various metabolic pathways. The central role of mTOR in metabolic rewiring makes it a promising target for cancer therapy. Numerous clinical trials are ongoing to evaluate the efficacy of mTOR inhibition for cancer treatment. Rapamycin analogs have been approved to treat specific types of cancer. Since rapamycin does not fully inhibit mTOR activity, new compounds have been engineered to inhibit the catalytic activity of mTOR to more potently block its functions. Despite highly promising pre-clinical studies, early clinical trial results of these second generation mTOR inhibitors revealed increased toxicity and modest antitumor activity. The plasticity of metabolic processes and seemingly enormous capacity of malignant cells to salvage nutrients through various mechanisms make cancer therapy extremely challenging. Therefore, identifying metabolic vulnerabilities in different types of tumors would present opportunities for rational therapeutic strategies. Understanding how the different sources of nutrients are metabolized not just by the growing tumor but also by other cells from the microenvironment, in particular, immune cells, will also facilitate the design of more sophisticated and effective therapeutic regimen. In this review, we discuss the functions of mTOR in cancer metabolism that have been illuminated from pre-clinical studies. We then review key findings from clinical trials that target mTOR and the lessons we have learned from both pre-clinical and clinical studies that could provide insights on innovative therapeutic strategies, including immunotherapy to target mTOR signaling and the metabolic network in cancer.

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“…Antitumor effect of γδ T cells is increased by pre-exposition to rapamycin [92] Besides antigen-encoding RNA, mTOR inhibitors also enhance the anti-tumor effects of DNA vaccines [99]. TC-1 tumor cells were injected into C57BL/6 mice on day 0.…”

Section: Mtor Inhibitors and Antitumor Vaccinesmentioning

confidence: 99%

“…Besides antigen-encoding RNA, mTOR inhibitors also enhance the anti-tumor effects of DNA vaccines [ 99 ]. TC-1 tumor cells were injected into C57BL/6 mice on day 0.…”

Section: Combining Mtor Inhibitors and Immunotherapies In Cancer Tmentioning

confidence: 99%

Combining mTOR Inhibitors and T Cell-Based Immunotherapies in Cancer Treatment

Hage

Dormond

2021

Cancers

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mTOR regulates several processes that control tumor development, including cancer cell growth, angiogenesis and the immune response to tumor. Accordingly, mTOR inhibitors have been thoroughly explored in cancer therapy but have failed to provide long-lasting anticancer benefits. Several resistance mechanisms that counteract the antitumor effect of mTOR inhibitors have been identified and have highlighted the need to use mTOR inhibitors in combination therapies. In this context, emerging evidence has demonstrated that mTOR inhibitors, despite their immunosuppressive properties, provide anticancer benefits to immunotherapies. In fact, mTOR inhibitors also display immunostimulatory effects, in particular by promoting memory CD8+ T cell generation. Hence, mTOR inhibitors represent a therapeutic opportunity to promote antitumor CD8 responses and to boost the efficacy of different modalities of cancer immunotherapy. In this context, strategies to reduce the immunosuppressive activity of mTOR inhibitors and therefore to shift the immune response toward antitumor immunity will be useful. In this review, we present the different classes of mTOR inhibitors and discuss their effect on immune cells by focusing mainly on CD8+ T cells. We further provide an overview of the different preclinical studies that investigated the anticancer effects of mTOR inhibitors combined to immunotherapies.

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mTOR Inhibitors Can Enhance the Anti-Tumor Effects of DNA Vaccines through Modulating Dendritic Cell Function in the Tumor Microenvironment

Cited by 14 publications

References 39 publications

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

Targeting mTOR and Metabolism in Cancer: Lessons and Innovations

Combining mTOR Inhibitors and T Cell-Based Immunotherapies in Cancer Treatment

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