Autophagy inhibition upregulates CD4+ tumor infiltrating lymphocyte expression via miR‐155 regulation and TRAIL activation

Petanidis, Savvas; Domvri, Kalliopi; Kioseoglou, Efrosini; Anestakis, Doxakis; Freitag, Lutz; Zarogoulidis, Konstantinos; Hohenforst-Schmidt, Wolfgang; Eberhardt, Wilfried

doi:10.1016/j.molonc.2016.08.005

Cited by 40 publications

(30 citation statements)

References 51 publications

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“…Of note, recent findings have revealed that autophagy contributes to immunosuppressive-related chemoresistance and promotes the capability of the tumor to avoid immune detection [83, 84]. Along the same line, enhanced autophagy has been observed in advanced stages of metastatic diseases, characterized by low levels of tumor-infiltrating T lymphocytes (TILs) [85]. Although this area of research is still poorly explored, autophagy could be considered a critical process for counteracting CSCs resistance to immunotherapeutic approaches.…”

Section: Autophagy and Cancer Stem Cellsmentioning

confidence: 99%

Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications

et al. 2019

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Autophagy and mitophagy act in cancer as bimodal processes, whose differential functions strictly depend on cancer ontogenesis, progression, and type. For instance, they can act to promote cancer progression by helping cancer cells survive stress or, instead, when mutated or abnormal, to induce carcinogenesis by influencing cell signaling or promoting intracellular toxicity. For this reason, the study of autophagy in cancer is the main focus of many researchers and several clinical trials are already ongoing to manipulate autophagy and by this way determine the outcome of disease therapy. Since the establishment of the cancer stem cell (CSC) theory and the discovery of CSCs in individual cancer types, autophagy and mitophagy have been proposed as key mechanisms in their homeostasis, dismissal or spread, even though we still miss a comprehensive view of how and by which regulatory molecules these two processes drive cell fate. In this review, we will dive into the deep water of autophagy, mitophagy, and CSCs and offer novel viewpoints on possible therapeutic strategies, based on the modulation of these degradative systems. Facts • Autophagy plays a dual role in cancer as a tumor suppressor and promoter. • CSCs are usually characterized by a dysregulation of autophagy/mitophagy.

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Section: Autophagy and Cancer Stem Cellsmentioning

confidence: 99%

Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications

et al. 2019

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“…2a-c) These data suggest that autophagy plays a role as a negative regulator of in ammation by regulating the expression of in ammatory cytokines.MiR-155 Is Involved in the Cytokine Production of DCs Induced by Dysfunctional AutophagyEarlier we showed that the expression of miR-155 was decreased in DCs from active BD patients [8]. Moreover, miR-155 has been reported to be involved in autophagy regulation [17,[25][26][27]. A further experiment was carried out to investigate if miR-155 was associated with cytokine production by DCs induced by dysfunctional autophagy.…”

mentioning

confidence: 81%

Decreased MicroRNA-155 in Behcet’s disease leads to defective control of autophagy thereby stimulating excessive proinflammatory cytokine production

Liang

Zhou

Feng

et al. 2020

Preprint

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Background: Earlier we reported that the microRNA (miR)-155 expression in dendritic cells (DCs) from Behcet’s disease (BD) patients was decreased and affected cytokine production of DCs. In this study, we investigated the mechanisms whereby miR-155 regulates cytokine production by DCs.Methods: The formation of autophagosomes in DCs was detected by transmission electron microscopy. Western blotting was used to detect the protein levels of LC3, Beclin-1, P62, p-mTOR and p-Akt in DCs. TNF-α, IL-6 and IL-1β expression were investigated by ELISA. MiR-155 mimics were transfected to DCs to evaluate its effects on autophagy and cytokine production. RNA interference was used to downregulate the expression of TAB2.Results: The formation of autophagosomes was found in DCs of active BD patients. The expressions of LC3-Ⅱ, Beclin-1, P62, IL-6, IL-1β and TNF-α were significantly increased in DCs of active BD patients compared to that of healthy controls. The autophagy promoter (3-MA) and inhibitor (rapamycin) significantly decreased or increased the expression of TNF-α, IL-6 and IL-1β by DCs. The expression of LC3-Ⅱand Beclin-1 were significantly increased, but the expression of P62 proteins was decreased in DCs transfected with miR-155 mimics or after TAB2 was downregulated. The expression of TNF-α, IL-6 and IL-1β were decreased in DCs after miR-155 was upregulated or TAB2 was downregulated. The ratios of p-Akt/Akt and p-mTOR/mTOR were decreased in DCs after miR-155 was upregulated.Conclusions: These results suggest that miR-155 affects the production of TNF-α, IL-6 and IL-1β by DCs through activation of the Akt/mTOR signaling pathway and by affecting the process of autophagy.

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“…Thus, an EMT regulatory program for the exhaustion of CD8p tumor-infiltrating lymphocytes and immunosuppression of PD-L1 via the miR-200/ZEB1 axis is critical to tumor metastasis. Likewise, miR-155 functions as an immune system activator by blocking autophagy, which promotes the upregulation of CD4+ and infiltration of FoxP3+ tumor-infiltrating lymphocytes, which results in increased lung carcinoma chemosensitivity [ 41 ].…”

Section: Correlation Among Smoking Cancer and Expression Of Mirnmentioning

confidence: 99%

MicroRNAs in Smoking-Related Carcinogenesis: Biomarkers, Functions, and Therapy

Fujii

Shimada

Nakai

et al. 2018

JCM

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Long-term heavy cigarette smoking is a well-known high-risk factor for carcinogenesis in various organs such as the head and neck, lungs, and urinary bladder. Furthermore, cigarette smoking can systemically accelerate aging, and as the result, promoting carcinogenesis via changing the host microenvironment. Various inflammatory factors, hormones, and chemical mediators induced by smoking mediate carcinoma-related molecules and induce carcinogenesis. MicroRNAs (miRNAs) are a family of short noncoding RNA molecules that bind to mRNAs and inhibit their expression. Cigarette smoke induces the expression of various miRNAs, many of which are known to function in the post-transcriptional silencing of anticancer molecules, thereby leading to smoking-induced carcinogenesis. Analysis of expression profiles of smoking-induced miRNAs can help identify biomarkers for the diagnosis and prognosis of smoking-related cancers and prediction of therapeutic responses, as well as revealing promising therapeutic targets. Here, we introduce the most recent and useful findings of miRNA analyses focused on lung cancer and urinary bladder cancer, which are strongly associated with cigarette smoking, and discuss the utility of miRNAs as clinical biomarkers.

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Autophagy inhibition upregulates CD4+ tumor infiltrating lymphocyte expression via miR‐155 regulation and TRAIL activation

Cited by 40 publications

References 51 publications

Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications

Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications

Decreased MicroRNA-155 in Behcet’s disease leads to defective control of autophagy thereby stimulating excessive proinflammatory cytokine production

MicroRNAs in Smoking-Related Carcinogenesis: Biomarkers, Functions, and Therapy

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