Radiotherapy and cGAS/STING signaling: Impact on MDSCs in the tumor microenvironment

Kho, Vera M.; Mekers, Vera E.; Span, Paul N.; Bussink, Johan; Adema, Gosse J.

doi:10.1016/j.cellimm.2021.104298

Cited by 43 publications

(29 citation statements)

References 118 publications

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“…Furthermore, radiation can alter the TME and, instead of tilting to anti-cancer immunity, induce an immunosuppressive milieu. Several studies showed that radiation induces infiltration and aggregation of MDSCs [ 69 , 70 ], which contributes to the immunosuppressive TME through multiple pathways. The same STING pathway that contributes to the cancer adjuvanticity at least partially contributes to the aggregation of MDSCs in tumor tissues [ 71 ].…”

Section: Combination Of Radiation Therapy With Immunotherapymentioning

confidence: 99%

Combination strategies to maximize the benefits of cancer immunotherapy

et al. 2021

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Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine.

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Section: Combination Of Radiation Therapy With Immunotherapymentioning

confidence: 99%

Combination strategies to maximize the benefits of cancer immunotherapy

et al. 2021

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“…Cytosolic dsDNA is sensed by cyclic GMP-AMP (cGAMP) synthase (cGAS), resulting in cGAMP generation. Consequently, the STING–TBK1–IRF3 pathway (STING: stimulator of interferon genes; TBK1: TANK-binding kinase 1; IRF3: interferon regulatory factor 3) is activated, causing IFN-I production and its release from inside to outside the cell ( 27 ). The interaction between IFN-I and its receptor on DCs promotes DCs maturation, increases the expression of costimulatory molecules on DCs, and enhances the migration ability of DCs to tumor-draining lymph nodes, eventually promoting antitumor immunity mediated by CD8 + T cells ( 28 ).…”

Section: The Mechanism Of Ir-driven Icdmentioning

confidence: 99%

Immunogenic Cell Death Induction by Ionizing Radiation

et al. 2021

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Immunogenic cell death (ICD) is a form of regulated cell death (RCD) induced by various stresses and produces antitumor immunity via damage-associated molecular patterns (DAMPs) release or exposure, mainly including high mobility group box 1 (HMGB1), calreticulin (CRT), adenosine triphosphate (ATP), and heat shock proteins (HSPs). Emerging evidence has suggested that ionizing radiation (IR) can induce ICD, and the dose, type, and fractionation of irradiation influence the induction of ICD. At present, IR-induced ICD is mainly verified in vitro in mice and there is few clinical evidence about it. To boost the induction of ICD by IR, some strategies have shown synergy with IR to enhance antitumor immune response, such as hyperthermia, nanoparticles, and chemotherapy. In this review, we focus on the molecular mechanisms of ICD, ICD-promoting factors associated with irradiation, the clinical evidence of ICD, and immunogenic forms of cell death. Finally, we summarize various methods of improving ICD induced by IR.

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“…The breaking of DNA double-strand by radiation is the basic principle of radiotherapy. Thus, the antitumor immunity will be enhanced [137]. However, when the radiation quantity rises out of a threshold (10-12 Gy), the interferon will simulate 3 -repair exonuclease 1 (TREX1), which subsequently down-regulates the cGAS-STING signaling pathway and degrades cytosolic double-stranded DNA [138].…”

Section: The Potential Signaling Pathway Can Be Targetedmentioning

confidence: 99%

A Comparative and Comprehensive Review of Antibody Applications in the Treatment of Lung Disease

Song

2022

Life

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Antibodies are a type of protein produced by active B cells in response to antigen stimulation. A series of monoclonal antibodies and neutralizing antibodies have been invented and put into clinical use because of their high therapeutic effect and bright developing insight. Patients with cancer, infectious diseases, and autoimmune diseases can all benefit from antibody therapy. However, the targeting aspects and potential mechanisms for treating these diseases differ. In the treatment of patients with infectious diseases such as COVID-19, neutralizing antibodies have been proposed as reliable vaccines against COVID-19, which target the ACE2 protein by preventing virus entry into somatic cells. Monoclonal antibodies can target immune checkpoints (e.g., PD-L1 and CTLA-4), tyrosine kinase and subsequent signaling pathways (e.g., VEGF), and cytokines in cancer patients (e.g. IL-6 and IL-1β). It is debatable whether there is any connection between the use of antibodies in these diseases. It would be fantastic to discover the related points and explain the burden for the limitation of cross-use of these techniques. In this review, we provided a comprehensive overview of the use of antibodies in the treatment of infectious disease and cancer patients. There are also discussions of their mechanisms and history. In addition, we discussed our future outlook on the use of antibodies.

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Radiotherapy and cGAS/STING signaling: Impact on MDSCs in the tumor microenvironment

Cited by 43 publications

References 118 publications

Combination strategies to maximize the benefits of cancer immunotherapy

Combination strategies to maximize the benefits of cancer immunotherapy

Immunogenic Cell Death Induction by Ionizing Radiation

A Comparative and Comprehensive Review of Antibody Applications in the Treatment of Lung Disease

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