Targeting Myeloid-derived Suppressor Cells and Programmed Death Ligand 1 Confers Therapeutic Advantage of Ablative Hypofractionated Radiation Therapy Compared With Conventional Fractionated Radiation Therapy

Lan, Jie; Li, Rui; Yin, Lu; Deng, Lei; Gui, Jun; Chen, Bao-Qing; Zhou, Lin; Meng, Maobin; Huang, Qiaorong; Mo, Xianming; Wei, Yuquan; Lü, Bo; Dicker, Adam P.; Xue, Jianxin; Lü, You

doi:10.1016/j.ijrobp.2018.01.071

Cited by 92 publications

(76 citation statements)

References 34 publications

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“…On the other side, RT combined with immunotherapy can effectively weaken MDSCs function, eventually promoting lethal effects of CD8 + T cells in tumor. Targeting MDSCs recruitment and enhancing antitumor immunity are crucial for the therapeutic efficacy of ablative hypofractionated radiation therapy (AHFRT) . When combined with anti‐PD‐L1 immunotherapy, AHFRT was more potent for cancer treatment.…”

Section: The Effects Of Mdscs Upon Radiotherapymentioning

confidence: 99%

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Yin

Wang

et al. 2018

Intl Journal of Cancer

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Cancer progression is closely related to the tumor microenvironment in which the tumor exists, including surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, signaling molecules and the extracellular matrix. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can impact the growth and evolution of cancerous cells. One of major cell components in the tumor microenvironment is myeloid-derived suppressor cells (MDSCs), which promote tumor growth and metastasis directly or indirectly by recognizing other immune cells, producing cytokines and exerting their immunosuppression functions. MDSCs have emerged as major regulators of immune responses in cancer and key targets for treating cancer. There are many limitations and side-effect in approaches of conventional cancer therapy, including radiotherapy. It has grown up to be a burgeoning field that a combination of radiotherapy and immunotherapy applied to cancer therapy. Therefore, it is fundamental to explore the immune mechanism in the process of cancer treatment. Here, we reviewed the recent progress of MDSCs in roles of the tumor microenvironment and tumor radiotherapy.

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Section: The Effects Of Mdscs Upon Radiotherapymentioning

confidence: 99%

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Yin

Wang

et al. 2018

Intl Journal of Cancer

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“…In the clinical and research setting, a comprehensive understanding of IR and its ability to induce and modulate inflammation and the immune system remains largely in its infancy, but in order to improve patient survival, a better understanding is essential. In doing so, we may be able to better select patients who will benefit from RT, select the optimal RT dose and fractionation regimen, or be able to augment the response by altering the microenvironment with emerging targeted therapies and/or immunotherapies (Lan et al 2018; Zhang and Niedermann 2018). …”

Section: Introductionmentioning

confidence: 99%

Radiation, inflammation and the immune response in cancer

et al. 2018

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Radiation is an important component of cancer treatment with more than half of all patients receive radiotherapy during their cancer experience. While the impact of radiation on tumour morphology is routinely examined in the pre-clinical and clinical setting, the impact of radiation on the tumour microenvironment and more specifically the inflammatory/immune response is less well characterised. Inflammation is a key contributor to short- and long-term cancer eradication, with significant tumour and normal tissue consequences. Therefore, the role of radiation in modulating the inflammatory response is highly topical given the current wave of targeted and immuno-therapeutic treatments for cancer. This review provides a general overview of how radiation modulates the inflammatory and immune response-(i) how radiation induces the inflammatory/immune system, (ii) the cellular changes that take place, (iii) how radiation dose delivery affects the immune response, and (iv) a discussion on research directions to improve patient survival, reduce side effects, improve quality of life, and reduce financial costs in the immediate future. Harnessing the benefits of radiation on the immune response will enhance its maximal therapeutic benefit and reduce radiation-induced toxicity.

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“…It has been well-summarized that RT both promotes and inhibits MDSC function (36). In conventional fractionated IR, there is an increase in MDSCs in both clinical trials and animal models (19,22). However, high-dose ablative IR reduced the level of MDSCs (22).…”

Section: Discussionmentioning

confidence: 99%

“…In conventional fractionated IR, there is an increase in MDSCs in both clinical trials and animal models (19,22). However, high-dose ablative IR reduced the level of MDSCs (22). We found the same results in two HCC tumorbearing mouse models: (1) the higher the IR dose/fraction, the bigger the off-target effect (Figure 2); (2) the bigger the tumor, the higher the blood MDSCs (both G-MDSCs and M-MDSCs) (C-E) The bone marrow cells were harvested from C57BL/6 or Institute of Cancer Research (ICR) mice and co-cultured with CM from Hepa1-6 or H22 cells irradiated with different single doses (0, 2.5, 4, 6, or 8 Gy).…”

Section: Discussionmentioning

confidence: 99%

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Hypofractionated Irradiation Suppressed the Off-Target Mouse Hepatocarcinoma Growth by Inhibiting Myeloid-Derived Suppressor Cell-Mediated Immune Suppression

et al. 2020

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Targeting Myeloid-derived Suppressor Cells and Programmed Death Ligand 1 Confers Therapeutic Advantage of Ablative Hypofractionated Radiation Therapy Compared With Conventional Fractionated Radiation Therapy

Cited by 92 publications

References 34 publications

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Myeloid‐derived suppressor cells: Roles in the tumor microenvironment and tumor radiotherapy

Radiation, inflammation and the immune response in cancer

Hypofractionated Irradiation Suppressed the Off-Target Mouse Hepatocarcinoma Growth by Inhibiting Myeloid-Derived Suppressor Cell-Mediated Immune Suppression

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