Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling

Xu, Meng; Pu, Yang; Han, Dali; Shi, Yi; Cao, Xuezhi; Liang, Hua; Chen, Xiang; Li, Xiao Dong; Deng, Lu; Chen, Zhijian J.; Weichselbaum, Ralph R.; Fu, Yang Xin

doi:10.1016/j.immuni.2017.07.016

Cited by 245 publications

(227 citation statements)

References 53 publications

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“…In addition to its effect on ADCP of tumor cells by macrophages, CD47 blockade promotes the activation of tumor‐specific cytotoxic T cells by DCs or macrophages . Treatment of tumor‐bearing mice with blocking Abs to CD47 thus promoted the recognition of tumor‐derived DNA through the stimulator of interferon genes (STING) pathway .…”

Section: Blockade Of the Cd47‐sirpα Signaling System Has Antitumor Efmentioning

confidence: 99%

“…Treatment of tumor‐bearing mice with blocking Abs to CD47 thus promoted the recognition of tumor‐derived DNA through the stimulator of interferon genes (STING) pathway . Such recognition increased type I interferon production by DCs and enhanced the cross‐priming of tumor‐specific cytotoxic T cells . Tumor‐infiltrating macrophages were also found to participate in the cross‐priming of tumor‐specific cytotoxic T cells .…”

Section: Blockade Of the Cd47‐sirpα Signaling System Has Antitumor Efmentioning

confidence: 99%

“…50 In addition to its effect on ADCP of tumor cells by macrophages, CD47 blockade promotes the activation of tumor-specific cytotoxic T cells by DCs or macrophages. 40,44,[51][52][53] Treatment of tumor-bearing mice with blocking Abs to CD47 thus promoted the recognition of tumor-derived DNA through the stimulator of interferon genes (STING) pathway. 52 Such recognition increased type I interferon production by DCs and enhanced the cross-priming of tumor-specific cytotoxic T cells.…”

Section: Targeting Of Cd47mentioning

confidence: 99%

“…52 Such recognition increased type I interferon production by DCs and enhanced the cross-priming of tumor-specific cytotoxic T cells. 53 Tumor-infiltrating macrophages were also found to participate in the cross-priming of tumor-specific cytotoxic T cells. 51 Blockade of CD47-SIRPα interaction is thus thought to promote the phagocytosis of tumor cells by macrophages and DCs, which, in turn, activate tumor-specific cytotoxic T cells at the site of tumor rejection.…”

Section: Targeting Of Cd47mentioning

confidence: 99%

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CD47‐signal regulatory protein α signaling system and its application to cancer immunotherapy

et al. 2018

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Tumor cells evade immune surveillance through direct or indirect interactions with various types of immune cell, with much recent attention being focused on modifying immune cell responses as the basis for the development of new cancer treatments. Signal regulatory protein α (SIRPα) and CD47 are both transmembrane proteins that interact with each other and constitute a cell‐cell communication system. SIRPα is particularly abundant in myeloid cells such as macrophages and dendritic cells, whereas CD47 is expressed ubiquitously and its expression level is elevated in cancer cells. Recent studies have shown that blockade of CD47‐SIRPα interaction enhances the phagocytic activity of phagocytes such as macrophages toward tumor cells in vitro as well as resulting in the efficient eradication of tumor cells in a variety of xenograft or syngeneic mouse models of cancer. Moreover, CD47 blockade has been shown to promote the stimulation of tumor‐specific cytotoxic T cells by macrophages or dendritic cells. Biological agents, such as Abs and recombinant proteins, that target human CD47 or SIRPα have been developed and are being tested in preclinical models of human cancer or in clinical trials with cancer patients. Preclinical studies have also suggested that CD47 or SIRPα blockade may have a synergistic antitumor effect in combination with immune checkpoint inhibitors that target the adaptive immune system. Targeting of the CD47‐SIRPα signaling system is thus a promising strategy for cancer treatment based on modulation of both innate and acquired immune responses to tumor cells.

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Section: Blockade Of the Cd47‐sirpα Signaling System Has Antitumor Efmentioning

confidence: 99%

Section: Blockade Of the Cd47‐sirpα Signaling System Has Antitumor Efmentioning

confidence: 99%

Section: Targeting Of Cd47mentioning

confidence: 99%

Section: Targeting Of Cd47mentioning

confidence: 99%

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CD47‐signal regulatory protein α signaling system and its application to cancer immunotherapy

et al. 2018

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“…However, understanding the role of STING in DCs during bacterial infections is relevant, since DCs are more specialized in DNA sensing than macrophages [38]. The role of STING in DCs was investigated in a model of c-di-AMP-overexpressing Mtb infection, where increased production of IL-1α, IL-6 and TNFα was observed [16].…”

Section: Discussionmentioning

confidence: 99%

The cGAS/STING Pathway Is Important for Dendritic Cell Activation but Is Not Essential to Induce Protective Immunity against <b><i>Mycobacterium tuberculosis</i></b> Infection

et al. 2018

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Mycobacterium tuberculosis (Mtb) infection remains a major public health concern. The STING (stimulator of interferon genes) pathway contributes to the cytosolic surveillance of host cells. Most studies on the role of STING activation in Mtb infection have focused on macrophages. Moreover, a detailed investigation of the role of STING during Mtb infection in vivo is required. Here, we deciphered the involvement of STING in the activation of dendritic cells (DCs) and the host response to Mtb infection in vivo. In DCs, this adaptor molecule was important for Ifn-β expression and IL-12 production as well as for the surface expression of the activation markers CD40 and CD86. We also documented that Mtb DNA induces STING activation in murine fibroblasts. In vivo Mtb aerogenic infection induced the upregulation of the STING and cGAS (cyclic GMP-AMP synthase) genes, and Ifn-β pulmonary expression was dependent on both sensors. However, mice deficient for STING or cGAS presented a similar outcome to wild-type controls, with no major alterations in body weight gain, bacterial burden, or survival. Lung inflammation, proinflammatory cytokine production, and inflammatory cell recruitment were similar in STING- and cGAS-deficient mice compared to wild-type controls. In summary, although the STING pathway seems to be crucial for DC activation during Mtb infection, it is dispensable for host protection in vivo.

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Targeting immunogenic cell death in cancer

2020

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Immunogenic cell death (ICD) is a type of cancer cell death triggered by certain chemotherapeutic drugs, oncolytic viruses, physicochemical therapies, photodynamic therapy, and radiotherapy. It involves the activation of the immune system against cancer in immunocompetent hosts. ICD comprises the release of damage-associated molecular patterns (DAMPs) from dying tumor cells that result in the activation of tumor-specific immune responses, thus eliciting long-term efficacy of anticancer drugs by combining direct cancer cell killing and antitumor immunity. Remarkably, subcutaneous injection of dying tumor cells undergoing ICD has been shown to provoke anticancer vaccine effects in vivo. DAMPs include the cell surface exposure of calreticulin (CRT) and heat-shock proteins (HSP70 and HSP90), extracellular release of adenosine triphosphate (ATP), high-mobility group box-1 (HMGB1), type I IFNs and members of the IL-1 cytokine family. In this review, we discuss the cell death modalities connected to ICD, the DAMPs exposed during ICD, and the mechanism by which they activate the immune system. Finally, we discuss the therapeutic potential and challenges of harnessing ICD in cancer immunotherapy.

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Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling

Cited by 245 publications

References 53 publications

CD47‐signal regulatory protein α signaling system and its application to cancer immunotherapy

CD47‐signal regulatory protein α signaling system and its application to cancer immunotherapy

The cGAS/STING Pathway Is Important for Dendritic Cell Activation but Is Not Essential to Induce Protective Immunity against <b><i>Mycobacterium tuberculosis</i></b> Infection

Targeting immunogenic cell death in cancer

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