Radiation-induced decrease of CD8 + dendritic cells contributes to Th1/Th2 shift

Hu, Liu; Li, Bailong; Jia, Xiaojing; Ma, Yan; Gu, Yi-Jie; Zhang, Pei; Wang, Qun; Cai, Jianming; Cui, Jianguo; Gao, Fu; Yang, Yue

doi:10.1016/j.intimp.2017.03.013

Cited by 21 publications

(18 citation statements)

References 46 publications

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“…Exposure to ionizing radiation often reduces Th1 function, resulting in a Th1/Th2 imbalance that may affect the efficacy of cancer radiotherapy [ 8 , 9 ]. It has been reported that ionizing radiation induced a lasting Th2 immune response while depressing Th1 immune responses in experimental animals and atomic bomb survivors.…”

Section: Introductionmentioning

confidence: 99%

Effects of various radiation doses on induced T-helper cell differentiation and related cytokine secretion

Gao

Dong

Gong

et al. 2018

Journal of Radiation Research

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Exposure to ionizing radiation often induces T helper (Th) cell differentiation, resulting in an imbalance of Th1 and Th2 cellular subtypes, which can affect the efficacy of cancer radiotherapy. The aim of this study was to analyze differential expression of Th1, Th2 and Th3/Type 1 regulatory T cell (Tr1) subtype–related genes and cytokines in mouse thymocytes after high- and low-dose systemic radiation, using functional classification gene arrays and Elisa assays, and to explore the molecular mechanisms underlying radiation’s immune effects and their relationship with Th1/Th2 immunity. We found that expression of 8 genes was upregulated after LDR, while expression of 5 genes was downregulated. After HDR, 54 genes were upregulated and 3 genes were downregulated, including genes related to Th1, Th2 and Th3/Tr1 cellular subtypes, Th1/Th2-type immune response genes and transcription factor–related genes. In the foregoing results, LDR and HDR in the thymus induced opposite patterns of expression for Th1-, Th2- and Th3-type related cytokines TGF-β, C/EBP-β and TNF-α. We also found that expression of Interferon-γ (IFN-γ) and Interleukin-2 (IL-2), which have a moderating effect on immune function, was upregulated after LDR. Furthermore, the secretion of negative regulatory factors Interleukin-1β (IL-1β), Interleukin-4 (IL-4), transforming growth factor-β (TGF-β) and Interleukin-21 (IL-21) was reduced after LDR, but HDR produced the opposite effect and stimulated their expression. These findings suggest that LDR may induce a Th1-type immune response, while HDR may lead to a Th2-type immune response.

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Section: Introductionmentioning

confidence: 99%

Effects of various radiation doses on induced T-helper cell differentiation and related cytokine secretion

Gao

Dong

Gong

et al. 2018

Journal of Radiation Research

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“…A recent study observed a significant decrease of BDCA3 + DC in the blood of patients treated with conventional irradiation (10 Gy). Moreover, consistently, CD8 + DC, (a mouse equivalent of human BDA3 + DC), also decreased in peripheral blood, spleen, and LNs post 6 Gy radiation, indicating a repression of Th1 immunity caused by irradiation [94].…”

Section: Dendritic Cellsmentioning

confidence: 96%

Highlighting the Potential for Chronic Stress to Minimize Therapeutic Responses to Radiotherapy through Increased Immunosuppression and Radiation Resistance

Chen

Singh

2020

Cancers

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Ionizing radiation has been used in the treatment of cancer for more than 100 years. While often very effective, there is still a great effort in place to improve the efficacy of radiation therapy for controlling the progression and recurrence of tumors. Recent research has revealed the close interaction between nerves and tumor progression, especially nerves of the autonomic nervous system that are activated by a variety of stressful stimuli including anxiety, pain, sleep loss or depression, each of which is likely to be increased in cancer patients. A growing literature now points to a negative effect of chronic stressful stimuli in tumor progression. In this review article, we present data on the potential for adrenergic stress to influence the efficacy of radiation and in particular, its potential to influence the anti-tumor immune response, and the frequency of an “abscopal effect” or the shrinkage of tumors which are outside an irradiated field. We conclude that chronic stress can be a major impediment to more effective radiation therapy through mechanisms involving immunosuppression and increased resistance to radiation-induced tumor cell death. Overall, these data highlight the potential value of stress reduction strategies to improve the outcome of radiation therapy. At the same time, objective biomarkers that can accurately and objectively reflect the degree of stress in patients over prolonged periods of time, and whether it is influencing immunosuppression and radiation resistance, are also critically needed.

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“…In head-and-neck cancer patients, neoadjuvant treatment was associated with a general decrease of tumor infiltrating DCs in intraepithelial compartments as assessed by IHC ( 154 ). In a study from Liu et al, authors found a significant decrease of BDCA3+ DCs, the immune-stimulatory variant, in the blood of patients treated with conventional radiotherapy ( 155 ).…”

Section: Effect Of Local Radiation On Inflammatory Cellsmentioning

confidence: 99%

Radiation-Induced Transformation of Immunoregulatory Networks in the Tumor Stroma

2018

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The implementation of novel cancer immunotherapies in the form of immune checkpoint blockers represents a major advancement in the treatment of cancer, and has renewed enthusiasm for identifying new ways to induce antitumor immune responses in patients. Despite the proven efficacy of neutralizing antibodies that target immune checkpoints in some refractory cancers, many patients do not experience therapeutic benefit, possibly owing to a lack of antitumor immune recognition, or to the presence of dominant immunosuppressive mechanisms in the tumor microenvironment (TME). Recent developments in this field have revealed that local radiotherapy (RT) can transform tumors into in situ vaccines, and may help to overcome some of the barriers to tumor-specific immune rejection. RT has the potential to ignite tumor immune recognition by generating immunogenic signals and releasing neoantigens, but the multiple immunosuppressive forces in the TME continue to represent important barriers to successful tumor rejection. In this article, we review the radiation-induced changes in the stromal compartments of tumors that could have an impact on tumor immune attack. Since different RT regimens are known to mediate strikingly different effects on the multifarious elements of the tumor stroma, special emphasis is given to different RT schedules, and the time after treatment at which the effects are measured. A better understanding of TME remodeling following specific RT regimens and the window of opportunity offered by RT will enable optimization of the design of novel treatment combinations.

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Radiation-induced decrease of CD8 + dendritic cells contributes to Th1/Th2 shift

Cited by 21 publications

References 46 publications

Effects of various radiation doses on induced T-helper cell differentiation and related cytokine secretion

Effects of various radiation doses on induced T-helper cell differentiation and related cytokine secretion

Highlighting the Potential for Chronic Stress to Minimize Therapeutic Responses to Radiotherapy through Increased Immunosuppression and Radiation Resistance

Radiation-Induced Transformation of Immunoregulatory Networks in the Tumor Stroma

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