Radiotherapy and the immune system: More than just immune suppression

Rückert, Michael; Flohr, Ann-Sophie; Hecht, Markus; Gaipl, Udo S.

doi:10.1002/stem.3391

Cited by 66 publications

(44 citation statements)

References 100 publications

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“…Except the direct damage to irradiated tumor cells, ionizing radiation (IR) also induces a series of biological effects which are deemed to be systemic, immune-mediated antitumor effects. 72 – 80 In fact, the immunomodulatory effects of IR are exactly theoretical basis of combination. IR can exert a potent antitumor immune response by influencing almost all steps in the cancer-immunity cycle rather than just several discrete steps with ICIs.…”

Section: Rationale Of Irtmentioning

confidence: 99%

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang

Liu

Chen

et al. 2022

Sig Transduct Target Ther

183

141

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Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which is called abscopal effect. The view of RT as a simple local treatment has dramatically changed in recent years, and it is now widely accepted that RT can provoke a systemic immune response which gives a strong rationale for the combination of RT and immunotherapy (iRT). Nevertheless, several points remain to be addressed such as the interaction of RT and immune system, the identification of the best schedules for combination with immunotherapy (IO), the expansion of abscopal effect and the mechanism to amplify iRT. To answer these crucial questions, we roundly summarize underlying rationale showing the whole immune landscape in RT and clinical trials to attempt to identify the best schedules of iRT. In consideration of the rarity of abscopal effect, we propose that the occurrence of abscopal effect induced by radiation can be promoted to 100% in view of molecular and genetic level. Furthermore, the “radscopal effect” which refers to using low-dose radiation to reprogram the tumor microenvironment may amplify the occurrence of abscopal effect and overcome the resistance of iRT. Taken together, RT could be regarded as a trigger of systemic antitumor immune response, and with the help of IO can be used as a radical and systemic treatment and be added into current standard regimen of patients with metastatic cancer.

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Section: Rationale Of Irtmentioning

confidence: 99%

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang

Liu

Chen

et al. 2022

Sig Transduct Target Ther

183

141

View full text Add to dashboard Cite

show abstract

“…More than 60% of tumor patients need radiotherapy, yet the radiation resistance of some tumor types and decreased radiotherapy sensitivity of intratumor hypoxic areas largely account for the failure of radiotherapy ( 45 – 47 ). Engineered E. coli (5 × 10 7 colony-forming unit (CFU)) cooperated with different doses of radiation (0, 8, 15, and 21 Gy).…”

Section: Bacteria-mediated Combined Cancer Treatmentmentioning

confidence: 99%

Bacteria−Based Synergistic Therapy in the Backdrop of Synthetic Biology

et al. 2022

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Although the synergistic effect of traditional therapies combined with tumor targeting or immunotherapy can significantly reduce mortality, cancer remains the leading cause of disease related death to date. Limited clinical response rate, drug resistance and off-target effects, to a large extent, impede the ceilings of clinical efficiency. To get out from the dilemmas mentioned, bacterial therapy with a history of more than 150 years regained great concern in recent years. The rise of biological engineering and chemical modification strategies are able to optimize tumor bacterial therapy in highest measure, and meanwhile avoid its inherent drawbacks toward clinical application such as bacteriotoxic effects, weak controllability, and low security. Here, we give an overview of recent studies with regard to bacteria-mediated therapies combined with chemotherapy, radiotherapy, and immunotherapy. And more than that, we review the bacterial detoxification and targeting strategies via biological reprogramming or chemical modification, their applications, and clinical transformation prospects.

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“…As a local therapy, radiation therapy is not effective in the treatment of extensively metastatic tumors, a major reason for cancer-induced mortality. − In addition, radiation therapy causes systemic immune suppression and dose-limiting side effects. − As a result, despite numerous attempts, the combination of radiation therapy and immune checkpoint blockade has not produced the anticipated clinical benefits in randomized controlled trials …”

Section: Radiotherapy–radiodynamic Therapymentioning

confidence: 99%

Nanoscale Metal–Organic Layers for Biomedical Applications

Luo

Lin

2021

Acc. Mater. Res.

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Conspectus As a monolayer version of nanoscale metal organic frameworks (nMOFs), nanoscale metal–organic layers (nMOLs) have recently emerged as a novel class of two-dimensional (2D) molecular nanomaterials. nMOLs are built from metal-oxo secondary building units (SBUs) with suitable coordination modes and organic linkers with proper geometries in a bottom-up fashion by carefully controlling the reaction temperature, capping agents, water concentration, and other parameters. M6-BTB and related nMOLs are formed by linking M6(μ3-O)4(μ3-OH)4 (M = Zr4+, Hf4+, Ce4+) SBUs and planar tricarboxylate bridging ligands such as 1,3,5-benzene-tribenzoate (BTB), while M12-nMOLs are constructed from M12(μ3-O)8(μ3-OH)8 (μ2-OH)6 (M = Zr4+, Hf4+) SBUs and linear dicarboxylate ligands such as 5,15-di(p-benzoato)porphyrin (DBP). Mechanistic studies revealed the important roles of capping agents and water on the growth of nMOLs and the stepwise growth process involving the partial hydrolysis of metal ions to form metal-oxo clusters with capping agents and the subsequent replacement of capping agents by bridging ligands. The 2D nature of nMOLs facilitates the postsynthetic modification of bridging ligands and the exchange of capping agents to simultaneously incorporate multifunctionalities into nMOLs. In this Account, we discuss the design principles, growth mechanisms, and postsynthetic functionalization strategies for nMOLs and summarize our research efforts to design nMOLs for various biological and biomedical applications. We first outline the strategies for the design and synthesis of M6- and M12-nMOLs via a dimensional reduction strategy and discuss the growth mechanisms of nMOLs. We then highlight the methods for the postsynthetic functionalization of nMOLs. We demonstrate the application of nMOLs in two broad categories. We first show the design and development of nMOLs for radiotherapy–radiodynamic therapy (RT–RDT) and further combination with checkpoint blockade immunotherapy. The evolution of Hf6-nMOLs to Hf12-nMOLs illustrates the control of nMOL morphology and photosensitizer loading for optimal RT–RDT effects. The nMOL-mediated RT–RDT is further combined with checkpoint blockade cancer immunotherapy to enable the treatment of systemic diseases via local X-ray irradiation. We next demonstrate nMOLs as a versatile platform for ratiometric sensing/imaging and drug delivery. The easily accessible sites on SBUs and ligands in nMOLs provide conjugation sites for multifunctional sensors and drugs, allowing for simultaneous ratiometric sensing of the pH and oxygen concentration or pH and glutathione concentration in mitochondria as well as highly effective photodynamic therapy with insoluble conjugated zinc phthalocyanine. We discuss the limitations of currently available nMOLs in terms of a lack of structural diversity and lower stability compared to nMOFs. We also point out the untapped potential of using the inherent hierarchy of SBU and bridging ligand structures to integrate multiple functionalities for synergistic func...

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Radiotherapy and the immune system: More than just immune suppression

Cited by 66 publications

References 100 publications

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Bacteria−Based Synergistic Therapy in the Backdrop of Synthetic Biology

Nanoscale Metal–Organic Layers for Biomedical Applications

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