Combining radiation therapy and cancer immune therapies: From preclinical findings to clinical applications

Bockel, S.; Durand, Bernard; Deutsch, Éric

doi:10.1016/j.canrad.2018.07.136

Cited by 26 publications

(25 citation statements)

References 113 publications

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“…Hsp70, translocated from the cytoplasm to the extracellular matrix, activates monocytes, macrophages, and DCs by binding to CD14, CD40, CD91, Lox1, and Toll-like receptors (TLR2 and TLR4) [37]. CRT, by binding to CD91 receptors present on DCs or macrophages, stimulates the phagocytosis of TAA and its presentation on MHC-1 [69,70]. Furthermore, IR upregulates the NK pathway by the activation of NKG2D ligands [33,70], increases NK cell cytotoxicity, tumor infiltration, and the production of many cytokines [71].…”

Section: Tumor Milieu As a Critical Immune Mediator Of Rtmentioning

confidence: 99%

“…IR also induces the production of IFN (type I) by activating a stimulator of interferon genes (STING) pathway in tumor-infiltrating DCs, as well as the increased secretion of CXCL10, a C-X-C chemokine receptor (CXCR3 + ) that recruits IFN-γ secreting CD8+ T cells [34,75]. STING protein is activated by cyclic GMP-AMP (cGAMP) produced by cGAMP synthase (cGAS), which detects dsDNA fragments in irradiated cancer cells [34,45,70,76]. Binding of cGAMP by STING activates a number of transcription factors like NF-κB, IRF3, IRF7 STAT3, and STAT6, which stimulate the immune system to respond against pathogens and cancer cells [77,78].…”

Section: Tumor Milieu As a Critical Immune Mediator Of Rtmentioning

confidence: 99%

“…Type I IFN stimulates DCs to present tumor-associated antigens to T lymphocytes, thereby activating the specific T-cell response both within the irradiated site and in the lymph nodes. Activated T cells and NK cells secrete type II IFN, i.e., IFN-γ, which triggers the expression of MHC-I on the surface of tumor cells [52,70].…”

Section: Tumor Milieu As a Critical Immune Mediator Of Rtmentioning

confidence: 99%

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Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

Jarosz-Biej

Smolarczyk

Cichoń

et al. 2019

IJMS

345

259

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Radiotherapy (RT), besides cancer cells, also affects the tumor microenvironment (TME): tumor blood vessels and cells of the immune system. It damages endothelial cells and causes radiation-induced inflammation. Damaged vessels inhibit the infiltration of CD8+ T lymphocytes into tumors, and immunosuppressive pathways are activated. They lead to the accumulation of radioresistant suppressor cells, including tumor-associated macrophages (TAMs) with the M2 phenotype, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). The area of tumor hypoxia increases. Hypoxia reduces oxygen-dependent DNA damage and weakens the anti-cancer RT effect. It activates the formation of new blood vessels and leads to cancer relapse after irradiation. Irradiation may also activate the immune response through immunogenic cell death induction. This leads to the “in situ” vaccination effect. In this article, we review how changes in the TME affect radiation-induced anticancer efficacy. There is a very delicate balance between the activation of the immune system and the immunosuppression induced by RT. The effects of RT doses on immune system reactions and also on tumor vascularization remain unclear. A better understanding of these interactions will contribute to the optimization of RT treatment, which may prevent the recurrence of cancer.

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Section: Tumor Milieu As a Critical Immune Mediator Of Rtmentioning

confidence: 99%

Section: Tumor Milieu As a Critical Immune Mediator Of Rtmentioning

confidence: 99%

Section: Tumor Milieu As a Critical Immune Mediator Of Rtmentioning

confidence: 99%

See 1 more Smart Citation

Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

Jarosz-Biej

Smolarczyk

Cichoń

et al. 2019

IJMS

345

259

View full text Add to dashboard Cite

show abstract

“…Several recent reviews have discussed the potential of combining immunotherapy and radiotherapy, including for lung cancer, with respect to clinical efficacy [37,38,39,40,41,42,43,44,45]. The recent review from Ko et al published in June 2018 nicely summarizes planned and ongoing trials of combined radioimmunotherapy in patients with NSCLC with respect to present knowledge [37].…”

Section: Combining Radiotherapy and Immunotherapy In Lung Cancermentioning

confidence: 99%

Combining Radiotherapy and Immunotherapy in Lung Cancer: Can We Expect Limitations Due to Altered Normal Tissue Toxicity?

Wirsdörfer

Leve

Jendrossek

2018

IJMS

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In recent decades, technical advances in surgery and radiotherapy, as well as breakthroughs in the knowledge on cancer biology, have helped to substantially improve the standard of cancer care with respect to overall response rates, progression-free survival, and the quality of life of cancer patients. In this context, immunotherapy is thought to have revolutionized the standard of care for cancer patients in the long term. For example, immunotherapy approaches such as immune checkpoint blockade are currently increasingly being used in cancer treatment, either alone or in combination with chemotherapy or radiotherapy, and there is hope from the first clinical trials that the appropriate integration of immunotherapy into standard care will raise the success rates of cancer therapy to a new level. Nevertheless, successful cancer therapy remains a major challenge, particularly in tumors with either pronounced resistance to chemotherapy and radiation treatment, a high risk of normal tissue complications, or both, as in lung cancer. Chemotherapy, radiotherapy and immunotherapy have the capacity to evoke adverse effects in normal tissues when administered alone. However, therapy concepts are usually highly complex, and it is still not clear if combining immunotherapy with radio(chemo)therapy will increase the risk of normal tissue complications, in particular since normal tissue toxicity induced by chemotherapy and radiotherapy can involve immunologic processes. Unfortunately, no reliable biomarkers are available so far that are suited to predict the unique normal tissue sensitivity of a given patient to a given treatment. Consequently, clinical trials combining radiotherapy and immunotherapy are attracting major attention, not only regarding efficacy, but also with regard to safety. In the present review, we summarize the current knowledge of radiation-induced and immunotherapy-induced effects in tumor and normal tissue of the lung, and discuss the potential limitations of combined radio-immunotherapy in lung cancer with a focus on the suspected risk for enhanced acute and chronic normal tissue toxicity.

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“…A large number of studies have investigated the complex interaction between radiation and the immune system, which has led to the emergence of the radio-immunobiology (47). The most prominent example of this interaction is observation of the “abscopal effect” where irradiation against a primary tumor results in the regression of metastatic clones in disparate areas of the body.…”

Section: Combining Immunotherapy With Radiotherapymentioning

confidence: 99%

Temozolomide Induced Hypermutation in Glioma: Evolutionary Mechanisms and Therapeutic Opportunities

et al. 2019

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Glioma are the most common type of malignant brain tumor, with glioblastoma (GBM) representing the most common and most lethal type of glioma. Surgical resection followed by radiotherapy and chemotherapy using the alkylating agent Temozolomide (TMZ) remain the mainstay of treatment for glioma. While this multimodal regimen is sufficient to temporarily eliminate the bulk of the tumor mass, recurrence is inevitable and often poses major challenges for clinical management due to treatment resistance and failure to respond to targeted therapies. Improved tumor profiling capacity has enabled characterization of the genomic landscape of gliomas with the overarching goal to identify clinically relevant subtypes and inform treatment decisions. Increased tumor mutational load has been shown to correlate with higher levels of neoantigens and is indicative of the potential to induce a durable response to immunotherapy. Following treatment with TMZ, a subset of glioma has been identified to recur with increased tumor mutational load. These hypermutant recurrent glioma represent a subtype of recurrence with unique molecular vulnerabilities. In this review, we will elaborate on the current knowledge regarding the evolution of hypermutation in gliomas and the potential therapeutic opportunities that arise with TMZ-induced hypermutation in gliomas.

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Combining radiation therapy and cancer immune therapies: From preclinical findings to clinical applications

Cited by 26 publications

References 113 publications

Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

Tumor Microenvironment as A “Game Changer” in Cancer Radiotherapy

Combining Radiotherapy and Immunotherapy in Lung Cancer: Can We Expect Limitations Due to Altered Normal Tissue Toxicity?

Temozolomide Induced Hypermutation in Glioma: Evolutionary Mechanisms and Therapeutic Opportunities

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