Dying of Stress: Chemotherapy, Radiotherapy, and Small-Molecule Inhibitors in Immunogenic Cell Death and Immunogenic Modulation

Fabian, Kellsye P.; Kowalczyk, Joshua T.; Reynolds, Sandy T.; Hodge, James W.

doi:10.3390/cells11233826

Cited by 11 publications

(5 citation statements)

References 181 publications

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“… 128 Furthermore, chemotherapy and radiotherapy can upregulate the antigen processing machinery, promote the expression of MHC class I, and elicit the expression of death receptors, rendering the tumor cells that survived the treatment more susceptible to immune attack ( Figure 2a ). 129 , 130 Several preclinical studies, including those on ICI-resistant tumor models, demonstrate that induction of ICD can potentiate the efficacy of ICI therapy. 131–133 The exact role of ICD is yet to be elucidated in a clinical setting, but growing evidence suggests that ICD inducers may play an important role in the antitumor effect of ICIs.…”

Section: Strategies To Overcome Associated Mechanisms Contributing To...mentioning

confidence: 99%

A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance

Santiago-Sánchez,

Fabian,

Hodge

2024

Cancer Biology & Therapy

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The discovery of immune checkpoints and the development of immune checkpoint inhibitors (ICI) have achieved a durable response in advanced-stage cancer patients. However, there is still a high proportion of patients who do not benefit from ICI therapy due to a lack of response when first treated (primary resistance) or detection of disease progression months after objective response is observed (acquired resistance). Here, we review the current FDA-approved ICI for the treatment of certain solid malignancies, evaluate the contrasting responses to checkpoint blockade in different cancer types, explore the known mechanisms associated with checkpoint blockade resistance (CBR), and assess current strategies in the field that seek to overcome these mechanisms. In order to improve current therapies and develop new ones, the immunotherapy field still has an unmet need in identifying other molecules that act as immune checkpoints, and uncovering other mechanisms that promote CBR.

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Section: Strategies To Overcome Associated Mechanisms Contributing To...mentioning

confidence: 99%

A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance

Santiago-Sánchez,

Fabian,

Hodge

2024

Cancer Biology & Therapy

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“…Additionally, there were two “basket trials” consisting of multiple solid tumors. The role of ICD in clinical application is important but remains difficult to evaluate owing to limited induction protocols, inaccurate monitoring indicators, and limited access to samples ( Fabian et al, 2022 ; Rapoport and Anderson, 2019 ). Most previous prospective clinical trials have used ICD as an exploratory endpoint and supported the beneficial effects of ICD in the prognosis of some patients with cancer ( Fu et al, 2022 ; Wang Y. et al, 2022 ).…”

Section: Clinical Applicationmentioning

confidence: 99%

Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot

Han,

Tian,

Zhai

et al. 2024

Front. Cell Dev. Biol.

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Immunotherapy has emerged as a promising cancer treatment option in recent years. In immune “hot” tumors, characterized by abundant immune cell infiltration, immunotherapy can improve patients’ prognosis by activating the function of immune cells. By contrast, immune “cold” tumors are often less sensitive to immunotherapy owing to low immunogenicity of tumor cells, an immune inhibitory tumor microenvironment, and a series of immune-escape mechanisms. Immunogenic cell death (ICD) is a promising cellular process to facilitate the transformation of immune “cold” tumors to immune “hot” tumors by eliciting innate and adaptive immune responses through the release of (or exposure to) damage-related molecular patterns. Accumulating evidence suggests that various traditional therapies can induce ICD, including chemotherapy, targeted therapy, radiotherapy, and photodynamic therapy. In this review, we summarize the biological mechanisms and hallmarks of ICD and introduce some newly discovered and technologically innovative inducers that activate the immune system at the molecular level. Furthermore, we also discuss the clinical applications of combing ICD inducers with cancer immunotherapy. This review will provide valuable insights into the future development of ICD-related combination therapeutics and potential management for “cold” tumors.

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“…Apoptosis induced by chemotherapy, but also by endoplasmic reticulum stress of tumor cells, triggers signaling mechanisms that affect anti-tumor antigen-specific T cells and thus induce an "in situ vaccination" effect. At the same time, chemotherapy can relatively avoid the destruction of CD8+ and CD4+ T cells and of NK cells, but it contributes to the depletion of stromal components and MDSC, through this TME modulation effect, increasing the tumor response to immunotherapy [34][35][36][37].…”

Section: Radiotherapy and Immunotherapy: Abscopal And "In Situ" Vacci...mentioning

confidence: 99%

Radiotherapy and Immunotherapy—A Future Partnership towards a New Standard

Mireștean

Iancu

2023

Applied Sciences

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The impressive results in terms of survival brought by immune checkpoint inhibitors (ICI) in metastatic malignant melanoma and the transformation of this disease with a poor prognosis into a chronic disease even with long-term survival cases have opened horizons for a new era in cancer treatments. Later, therapy with CTLA-4 and PD-1/PD-L1 inhibitors became standard in other solid tumors, especially in relapsed and metastatic settings. The PACIFIC clinical trial revolutionized the concept of consolidation immunotherapy after the favorable response to curative chemoradiotherapy in non-small cell lung carcinoma (NSCLC). Two new effects will govern the future of the immunotherapy–radiotherapy association: the local “in situ” vaccination effect and the systemic remote “abscopal” response. Even if stereotactic body irradiation (SBRT) or stereotactic radiosurgery (SRT) seems to be more effective in generating the synergistic effect, the PACIFIC trial demonstrates the role of conventional irradiation in combination with chemotherapy in modulating the host’s immune response. Thus, the radiotherapy–chemotherapy–immunotherapy triad may become the future standard in locally advanced disease. The different mechanisms of producing immune-mediated cell death and the indirect role of augmenting the immune effect induced by radiotherapy make the old theories related to the therapeutic sequence, fractionation, doses, and target volumes as well as the protection of healthy tissues to be re-evaluated. The new concept of immuno-radiotherapy in synergistic association has as its physiopathological substrate the dual immunosuppressive and enhancement of antitumor response to irradiation, including the activation of the immune effectors in the tumor microenvironment (TME). The choice of sequential treatment, a hypofractionated irradiation regime, and the possible omission of lymph node irradiation with the limitation of lymphopenia could tilt the balance in favor of the activation and potentiation of the antitumor immune response. The selection of therapeutic targets chosen for the combination of immunotherapy and associated radiotherapy can be conducted based on the classification of tumors in the three immune phenotypes that characterize “cold” and “hot” tumors from the point of view of the response to therapy.

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Dying of Stress: Chemotherapy, Radiotherapy, and Small-Molecule Inhibitors in Immunogenic Cell Death and Immunogenic Modulation

Cited by 11 publications

References 181 publications

A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance

A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance

Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot

Radiotherapy and Immunotherapy—A Future Partnership towards a New Standard

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