Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Monaci, Sara; Coppola, Federica; Giuntini, Gaia; Roncoroni, Rossella; Acquati, Francesco; Sozzani, Silvano; Carraro, Fabio; Naldini, Antonella

doi:10.3390/ijms22147564

Cited by 12 publications

(6 citation statements)

References 36 publications

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“…Similarly, hypoxia negatively affects DC cells function which is associated with HIF-1α accumulation and DC cells’ autophagy/apoptosis regulated by the PI3K/AKT pathway. 284 …”

Section: Autophagy Antagonizes the Antitumor Immune Responsementioning

confidence: 99%

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Gao

Wang

Zhou

et al. 2022

Sig Transduct Target Ther

293

103

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In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not to ICIs, partly caused by the absence of tumor-infiltrating lymphocytes (TILs), significantly limits the application of ICIs. Converting these immune “cold” tumors into “hot” tumors that may respond to ICIs is an unsolved question in cancer immunotherapy. Since it is a general characteristic of cancers to resist apoptosis, induction of non-apoptotic regulated cell death (RCD) is emerging as a new cancer treatment strategy. Recently, several studies have revealed the interaction between non-apoptotic RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, and necroptosis exhibit synergistic antitumor immune responses while possibly exerting inhibitory effects on antitumor immune responses. Thus, targeted therapies (inducers or inhibitors) against autophagy, ferroptosis, pyroptosis, and necroptosis in combination with immunotherapy may exert potent antitumor activity, even in tumors resistant to ICIs. This review summarizes the multilevel relationship between antitumor immunity and non-apoptotic RCD, including autophagy, ferroptosis, pyroptosis, and necroptosis, and the potential targeting application of non-apoptotic RCD to improve the efficacy of immunotherapy in malignancy.

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“…Similarly, hypoxia negatively affects DC cells function which is associated with HIF-1α accumulation and DC cells’ autophagy/apoptosis regulated by the PI3K/AKT pathway. 284 …”

Section: Autophagy Antagonizes the Antitumor Immune Responsementioning

confidence: 99%

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Gao

Wang

Zhou

et al. 2022

Sig Transduct Target Ther

293

103

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“…10,[34][35][36] Moreover, hypoxia plays a role in fostering an immunosuppressive tumor microenvironment, 37 also favoring cancer cell growth. 38,39 Emerging evidence supports an alternative effect of anti-angiogenic therapy by temporarily normalizing the aberrant structure of tumor vasculature, known as vascular normalization. [13][14][15] The tumor vessels are distinct from those in normal tissues and are characterized by excessive, dilated, tortuous, and hyperpermeable.…”

Section: Anti-angiogenic Therapymentioning

confidence: 99%

Anti‐angiogenic therapy enhances cancer immunotherapy: Mechanism and clinical application

Li,

Fang

2024

Interdisciplinary Medicine

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Immunotherapy, specifically immune checkpoint inhibitors, is revolutionizing cancer treatment, achieving durable control of previously incurable or advanced tumors. However, only a certain group of patients exhibit effective responses to immunotherapy. Anti‐angiogenic therapy aims to block blood vessel growth in tumors by depriving them of essential nutrients and effectively impeding their growth. Emerging evidence shows that tumor vessels exhibit structural and functional abnormalities, resulting in an immunosuppressive microenvironment and poor response to immunotherapy. Both preclinical and clinical studies have used anti‐angiogenic agents to enhance the effectiveness of immunotherapy against cancer. In this review, we concentrate on the synergistic effect of anti‐angiogenic and immune therapies in cancer management, dissect the direct effects and underlying mechanisms of tumor vessels on recruiting and activating immune cells, and discuss the potential of anti‐angiogenic agents to improve the effectiveness of immunotherapy. Lastly, we outline challenges and opportunities for the anti‐angiogenic strategy to enhance immunotherapy. Considering the increasing approval of the combination of anti‐angiogenic and immune therapies in treating cancers, this comprehensive review would be timely and important.

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“… 132 The hypoxic TME also promotes apoptosis of DCs by inhibiting the PI3K/Akt pathway. 133 Plasmacytoid DCs (pDCs) play immunosuppressive roles in the TME. Hypoxia-induced extracellular adenosine (ADO) significantly enhances pDCs recruitment into tumors.…”

Section: Hypoxia Regulated the Tme Of Crcmentioning

confidence: 99%

Prediction of immunotherapy efficacy and immunomodulatory role of hypoxia in colorectal cancer

et al. 2022

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Immunotherapy has been used in the clinical treatment of colorectal cancer (CRC); however, most patients fail to achieve satisfactory survival benefits. Biomarkers with high specificity and sensitivity are being increasingly developed to predict the efficacy of CRC immunotherapy. In addition to DNA alteration markers, such as microsatellite instability/mismatch repair and tumor mutational burden, immune cell infiltration and immune checkpoints (ICs), epigenetic changes and no-coding RNA, and gut microbiomes all show potential predictive ability. Recently, the hypoxic tumor microenvironment (TME) has been identified as a key factor mediating CRC immune evasion and resistance to treatment. Hypoxia-inducible factor-1α is the central transcription factor in the hypoxia response that drives the expression of a vast number of survival genes by binding to the hypoxia response element in cancer and immune cells in the TME. Hypoxia regulates angiogenesis, immune cell infiltration and activation, expression of ICs, and secretion of various immune molecules in the TME and is closely associated with the immunotherapeutic efficacy of CRC. Currently, various agents targeting hypoxia have been found to improve the TME and enhance the efficacy of immunotherapy. We reviewed current markers commonly used in CRC to predict therapeutic efficacy and the mechanisms underlying hypoxia-induced angiogenesis and tumor immune evasion. Exploring the mechanisms by which hypoxia affects the TME will assist the discovery of new immunotherapeutic predictive biomarkers and development of more effective combinations of agents targeting hypoxia and immunotherapy.

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Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Cited by 12 publications

References 36 publications

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Anti‐angiogenic therapy enhances cancer immunotherapy: Mechanism and clinical application

Prediction of immunotherapy efficacy and immunomodulatory role of hypoxia in colorectal cancer

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