Hyperthermia Targeting the Tumor Microenvironment Facilitates Immune Checkpoint Inhibitors

Li, Zihui; Deng, Jiehui; Sun, Jiazhong; Ma, Yanling

doi:10.3389/fimmu.2020.595207

Cited by 67 publications

(75 citation statements)

References 133 publications

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“…There is considerable evidence that hyperthermia potentiates the adjuvanticity of tumor cell immunogenicity; for example, by the release of many of the aforementioned DAMPs (reviewed in detail in subsequent sections). Several of the immunostimulatory effects of hyperthermia on the tumor microenvironment include an increased tumor perfusion and reoxygenization allowing for an enhanced immune-effector uptake and a decreased hypoxia-related immunosuppression, an increased immune cell trafficking and effector function and increased pro-inflammatory cytokines [ 38 , 39 ]. Furthermore, we have demonstrated that hyperthermia can modulate the myeloid population toward an M1 phenotype within the tumor microenvironment by altering the tumor-intrinsic Wnt -β-catenin pathway [ 40 ].…”

Section: Immunogenicity Of Ablation: It Starts With Immunogenic Cell Deathmentioning

confidence: 99%

Hyperthermia and Tumor Immunity

Adnan

Muñoz

Prakash

et al. 2021

Cancers

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Thermal ablation is a cornerstone in the management of cancer patients. Typically, ablation procedures are performed for patients with a solitary or oligometastatic disease with the intention of eradicating all sites of the disease. Ablation has traditionally played a less prominent role for patients with a widely metastatic disease. For such patients, attempting to treat numerous sites of disease compounds potential risks without a clear clinical benefit and, as such, a compelling justification for performing an intervention that is unlikely to alter a patient’s clinical trajectory is uncommon. However, the discovery of immune checkpoints and the development of immune checkpoint inhibitors have brought a new perspective to the relevance of local cancer therapies such as ablation for patients with a metastatic disease. It is becoming increasingly apparent that local cancer therapies can have systemic immune effects. Thus, in the new perspective of cancer care centered upon immunologic principles, there is a strong interest in exploring the utility of ablation for patients with a metastatic disease for its immunologic implications. In this review, we summarize the unmet clinical need for adjuvant interventions such as ablation to broaden the impact of systemic immunotherapies. We additionally highlight the extant preclinical and clinical data for the immunogenicity of common thermal ablation modalities.

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Section: Immunogenicity Of Ablation: It Starts With Immunogenic Cell Deathmentioning

confidence: 99%

Hyperthermia and Tumor Immunity

Adnan

Muñoz

Prakash

et al. 2021

Cancers

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“…The activation of anti-tumor immunity by radiotherapy has become well known recently, and synergistic use of immune checkpoint inhibitors and radiotherapy has the potential to improve survival [19]. Activation of anti-tumor immunity via heat shock proteins by hyperthermia has also been suggested in recent preclinical data [20]. The development of the combination therapy of re-irradiation therapy, hyperthermia and immune checkpoint inhibitors is expected to be useful in the treatment of recurrent nasopharyngeal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Salvage Re-irradiation with Intensity-modulated Radiotherapy, Chemotherapy Combined with Hyperthermia for Local Recurrence of Nasopharyngeal Carcinoma After Chemoradiotherapy

Morisaki

Ohguri

Yahara

et al. 2021

J UOEH

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A sufficient dose of radiation is difficult to administer in re-irradiation for local recurrence of cancer after radiotherapy because of the dose limitation to organs at risk. Re-irradiation cases also include radioresistant tumors that are difficult to control locally, and their prognosis is poor in general. The effect of re-irradiation using intensitymodulated radiotherapy (IMRT) has recently been reported to significantly reduce the dose to organs at risk, and the efficacy of hyperthermia has been reported for radioresistant tumors. We report a case of local recurrence after concurrent chemoradiotherapy treated with salvage re-irradiation using IMRT and chemotherapy combined with hyperthermia in a patient with nasopharyngeal carcinoma, and include a discussion of the literature.

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“…Hyperthermia (HT) is a cancer treatment strategy by raising tissue temperature to 39–45°C for a certain period of time and it has been reported in many phase II and phase III trials combined with radiotherapy and chemotherapy ( 88 , 89 ). HT can not only cause protein denaturation and aggregation to activate downstream pathways such as the DNA damage response to kill tumor cells directly but also induce ICD to reverse tumor immunosuppressive microenvironment and produce antitumor immunity ( 90 ).…”

Section: The Methods Of Enhancing Ir-induced 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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Hyperthermia Targeting the Tumor Microenvironment Facilitates Immune Checkpoint Inhibitors

Cited by 67 publications

References 133 publications

Hyperthermia and Tumor Immunity

Hyperthermia and Tumor Immunity

Salvage Re-irradiation with Intensity-modulated Radiotherapy, Chemotherapy Combined with Hyperthermia for Local Recurrence of Nasopharyngeal Carcinoma After Chemoradiotherapy

Immunogenic Cell Death Induction by Ionizing Radiation

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