Anti-tumor immunity influences cancer cell reliance upon ATG7

Arensman, Michael D.; Yang, Xiaoran; Zhong, Wenyan; Bisulco, Stephanie; Upeslacis, Erik; Rosfjord, Edward; Deng, Shibing; Abraham, Robert T.; Eng, Christina H.

doi:10.1080/2162402x.2020.1800162

Cited by 18 publications

(9 citation statements)

References 54 publications

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“…Recent study indicated that loss of ATG7 in cancer cells which mediates autophagy disruption can enhance antitumor immune responses. 67 Our data suggest that ATG7 demethylation was closely associated with immune exclusion and CAF infiltration, which may provide insights into possible mechanisms.…”

Section: Discussionmentioning

confidence: 59%

Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer

Zeng

Luo

et al. 2021

J Immunother Cancer

126

100

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BackgroundDurable efficacy of immune checkpoint blockade (ICB) occurred in a small number of patients with metastatic gastric cancer (mGC) and the determinant biomarker of response to ICB remains unclear.MethodsWe developed an open-source TMEscore R package, to quantify the tumor microenvironment (TME) to aid in addressing this dilemma. Two advanced gastric cancer cohorts (RNAseq, N=45 and NanoString, N=48) and other advanced cancer (N=534) treated with ICB were leveraged to investigate the predictive value of TMEscore. Simultaneously, multi-omics data from The Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD) and Asian Cancer Research Group (ACRG) were interrogated for underlying mechanisms.ResultsThe predictive capacity of TMEscore was corroborated in patient with mGC cohorts treated with pembrolizumab in a prospective phase 2 clinical trial (NCT02589496, N=45, area under the curve (AUC)=0.891). Notably, TMEscore, which has a larger AUC than programmed death-ligand 1 combined positive score, tumor mutation burden, microsatellite instability, and Epstein-Barr virus, was also validated in the multicenter advanced gastric cancer cohort using NanoString technology (N=48, AUC=0.877). Exploration of the intrinsic mechanisms of TMEscore with TCGA and ACRG multi-omics data identified TME pertinent mechanisms including mutations, metabolism pathways, and epigenetic features.ConclusionsCurrent study highlighted the promising predictive value of TMEscore for patients with mGC. Exploration of TME in multi-omics gastric cancer data may provide the impetus for precision immunotherapy.

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Section: Discussionmentioning

confidence: 59%

Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer

Zeng

Luo

et al. 2021

J Immunother Cancer

126

100

View full text Add to dashboard Cite

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“…In addition, conditions of “leaky gut” associated with the conditional ablation of Atg7 in epithelial colon cells predispose a local immune response that is instrumental for limiting the number of pre‐tumoral lesions in Apc + / − colonocytes (Levy et al , 2015 ). Consistently, CT26 cells knocked out for Atg7 show increased expression of chemokines involved in the recruitment of CD8 + T lymphocytes, and depletion of CD8 + T cells significantly restores the growth of tumors in immunocompetent hosts (Arensman et al , 2020 ).…”

Section: Cancermentioning

confidence: 84%

Autophagy in major human diseases

et al. 2021

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Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.

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“…However, the drug resistance of glioma was not studied in this study, so whether DANCR can affect drug resistance by regulating ATG7-induced autophagy needs to be further studied. A recent study in mice showed that ATG7-related autophagy promoted anti-tumor immunity, thereby promoting tumor-cell survival (42). Hypoxia in glioma cells can induce intracellular protective autophagy, thus affecting glioma progression (43).…”

Section: Discussionmentioning

confidence: 99%

DANCR promotes glioma cell autophagy and proliferation via the miR‑33b/DLX6/ATG7 axis

2023

Oncol Rep

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Long non-coding RNAs (lncRNAs) are common in the human body. Misregulated lncRNA expression can cause a variety of diseases in the human body. The present study aimed to investigate the effect of lncRNA differentiation antagonizing non-protein-coding RNA (DANCR) on glioma proliferation and autophagy through the microRNA (miR)-33b/distal-less homeobox 6 (DLX6)/autophagy-related 7 (ATG7) axis. Reverse transcription-quantitative PCR was used to detect DANCR and miR-33b expression. Cell Counting Kit-8 assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transmission electron microscopy was used to determine the autophagy level by observing intracellular autophagosomes. A western blot assay was used to detect protein expression levels and determine the level of autophagy in different cells. The binding sites of miR-33b and DANCR or DLX6 were detected using a dual-luciferase reporter assay. A chromatin immunoprecipitation assay confirmed DLX6 as a transcript of ATG7. In vivo tumorigenesis of glioma cells was validated in nude mice. DANCR and DLX6 were highly expressed in glioma cells, while miR-33b showed low expression in glioma cells. DANCR reduced the targeted binding of miR-33b to DLX6 by sponging miR-33b. The result verified that DANCR could promote ATG7 protein expression through miR-33b/DLX6, promote intracellular autophagy and proliferation and reduce apoptosis. The present study identified the role of the DANCR/miR-33b/DLX6/ATG7 axis in regulating autophagy, proliferation, and apoptosis in glioma cells, providing new ideas for glioma treatment.

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Anti-tumor immunity influences cancer cell reliance upon ATG7

Cited by 18 publications

References 54 publications

Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer

Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer

Autophagy in major human diseases

DANCR promotes glioma cell autophagy and proliferation via the miR‑33b/DLX6/ATG7 axis

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