High mobility group box 1 promotes radioresistance in esophageal squamous cell carcinoma cell lines by modulating autophagy

Ma, Hongbing; Zheng, Shuyu; Zhang, Xiaozhi; Gong, Tuotuo; Lv, Xin; Fu, Shihua; Zhang, Shuqun; Yin, Xiaonan; Hao, Jingcan; Shan, Changyou; Huang, Shan

doi:10.1038/s41419-019-1355-1

Cited by 32 publications

(32 citation statements)

References 20 publications

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“…However, the induction of ICD does not always abrogate tumor growthand may even induce tumor progression in some cancers. [20][21][22] Hence, determining the optimal doses, fractions and schedules of radiotherapy may help counter the negative effects of DAMPs after radiotherapy.…”

Section: Generation Of Immunogenic Cell Death After Radiotherapymentioning

confidence: 99%

“…Immunogenic DAMPs released as a consequence of radiotherapy act as potent inducers to prime innate and adaptive antitumor immune responses. However, the induction of ICD does not always abrogate tumor growth – and may even induce tumor progression in some cancers 20–22 . Hence, determining the optimal doses, fractions and schedules of radiotherapy may help counter the negative effects of DAMPs after radiotherapy.…”

Section: Generation Of Immunogenic Cell Death After Radiotherapymentioning

confidence: 99%

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Enhancing the efficacy of immunotherapy using radiotherapy

et al. 2020

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Recent clinical breakthroughs in cancer immunotherapy, especially with immune checkpoint blockade, offer great hope for cancer sufferersand have greatly changed the landscape of cancer treatment. However, whilst many patients achieve clinical responses, others experience minimal benefit or do not respond to immune checkpoint blockade at all. Researchers are therefore exploring multimodal approaches by combining immune checkpoint blockade with conventional cancer therapies to enhance the efficacy of treatment. A growing body of evidence from both preclinical studies and clinical observations indicates that radiotherapy could be a powerful driver to augment the efficacy of immune checkpoint blockade, because of its ability to activate the antitumor immune response and potentially overcome resistance. In this review, we describe how radiotherapy induces DNA damage and apoptosis, generates immunogenic cell death and alters the characteristics of key immune cells in the tumor microenvironment. We also discuss recent preclinical work and clinical trials combining radiotherapy and immune checkpoint blockade in thoracic and other cancers. Finally, we discuss the scheduling of immune checkpoint blockade and radiotherapy, biomarkers predicting responses to combination therapy, and how these novel data may be translated into the clinic.

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Section: Generation Of Immunogenic Cell Death After Radiotherapymentioning

confidence: 99%

Section: Generation Of Immunogenic Cell Death After Radiotherapymentioning

confidence: 99%

Enhancing the efficacy of immunotherapy using radiotherapy

et al. 2020

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“…Accumulated evidence showed that increased autophagy is an adaptive response that contributes to the acquisition of radiation resistance in cancer 27 . Indeed, we observed IR-resistant cells with high expression of KCNQ1OT1 enhanced autophagy activity compared to their parental cells.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of KCNQ1OT1 promotes resistance to stereotactic body radiotherapy in lung adenocarcinoma by inducing ATG5/ATG12-mediated autophagy via miR-372-3p

He¹,

Song

Yang

et al. 2020

Cell Death Dis

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Stereotactic body radiotherapy (SBRT) has emerged as a standard treatment for non-small-cell lung cancer. However, its therapeutic advantages are limited with the development of SBRT resistance. The SBRT-resistant cell lines (A549/IR and H1975/IR) were established after exposure with hypofractionated irradiation. The differential lncRNAs were screened by microarray assay, then the expression was detected in LUAD tumor tissues and cell lines by qPCR. The influence on radiation response was assessed via in vitro and in vivo assays, and autophagy levels were evaluated by western blot and transmission electron microscopy. Bioinformatics prediction and rescue experiments were used to identify the pathways underlying SBRT resistance. High expression of KCNQ1OT1 was identified in LUAD SBRT-resistant cells and tissues, positively associated with a large tumor, advanced clinical stage, and a lower response rate to concurrent therapy. KCNQ1OT1 depletion significantly resensitized A549/IR and H1975/IR cells to radiation by inhibiting autophagy, which could be attenuated by miR-372-3p knockdown. Furthermore, autophagy-related 5 (ATG5) and autophagy-related 12 (ATG12) were confirmed as direct targets of miR-372-3p. Restoration of either ATG5 or ATG12 abrogated miR-372-3p-mediated autophagy inhibition and radiosensitivity. Our data describe that KCNQ1OT1 is responsible for SBRT resistance in LUAD through induction of ATG5- and ATG12-dependent autophagy via sponging miR-372-3p, which would be a potential strategy to enhance the antitumor effects of radiotherapy in LUAD.

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“…In this context, activation of autophagy with the mTORC1 inhibitor rapamcyin augmented cell death in response to combination of nimotuzumab with either cisplatin or paclitaxel. In EAC, treatment with lapatinib, a small molecule inhibitor of EGFR, was associated with induction of autophagy in OE19 cells in vitro, and pharmacological autophagy inhibition potentiated lapatinib-mediated cytotoxicity [73]. Additionally, basal autophagy flux was elevated in Lapatinib-resistant OE19 cells as compared to parental controls, and cell viability was decreased by autophagy inhibition alone or in combination with lapatinib.…”

Section: Roles For Autophagy In Esophageal Cancer Responses To Thementioning

confidence: 99%

Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes

Saxena

Klochkova

Murray

et al. 2019

Cancers

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Esophageal cancer is among the most aggressive forms of human malignancy with five-year survival rates of <20%. Autophagy is an evolutionarily conserved catabolic process that degrades and recycles damaged organelles and misfolded proteins to maintain cellular homeostasis. While alterations in autophagy have been associated with carcinogenesis across tissues, cell type- and context-dependent roles for autophagy have been reported. Herein, we review the current knowledge related to autophagy in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), the two most common subtypes of esophageal malignancy. We explore roles for autophagy in the development and progression of ESCC and EAC. We then continue to discuss molecular markers of autophagy as they relate to esophageal patient outcomes. Finally, we summarize current literature examining roles for autophagy in ESCC and EAC response to therapy and discuss considerations for the potential use of autophagy inhibitors as experimental therapeutics that may improve patient outcomes in esophageal cancer.

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High mobility group box 1 promotes radioresistance in esophageal squamous cell carcinoma cell lines by modulating autophagy

Cited by 32 publications

References 20 publications

Enhancing the efficacy of immunotherapy using radiotherapy

Enhancing the efficacy of immunotherapy using radiotherapy

Upregulation of KCNQ1OT1 promotes resistance to stereotactic body radiotherapy in lung adenocarcinoma by inducing ATG5/ATG12-mediated autophagy via miR-372-3p

Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes

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