Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death

Hayashi, Kazukuni; Nikolos, Fotis; Lee, Y. C.; Jain, Antrix; Tsouko, Efrosini; Gao, Haiyan; Kasabyan, Armine; Leung, Hon‐Chiu Eastwood; Osipov, Arsen; Jung, Sung Yun; Kurtova, Antonina V.; Chan, Keith S.

doi:10.1038/s41467-020-19970-9

Cited by 180 publications

(135 citation statements)

References 71 publications

(145 reference statements)

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“…Different DAMPs can be released at the different stages even within the same type of cell death. During apoptosis, ATP is released at the pre-apoptotic stage while HMGB1 is released at the late stage [ 12 , 13 ]. Besides the preceding DAMPs, it still largely remains elusive and further studies are awaited as to the types and stages of the cell death of their origin.…”

Section: Universal Mechanisms Of Damp Releasementioning

confidence: 99%

Release mechanisms of major DAMPs

et al. 2021

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Damage-associated molecular patterns (DAMPs) are endogenous molecules which foment inflammation and are associated with disorders in sepsis and cancer. Thus, therapeutically targeting DAMPs has potential to provide novel and effective treatments. When establishing anti-DAMP strategies, it is important not only to focus on the DAMPs as inflammatory mediators but also to take into account the underlying mechanisms of their release from cells and tissues. DAMPs can be released passively by membrane rupture due to necrosis/necroptosis, although the mechanisms of release appear to differ between the DAMPs. Other types of cell death, such as apoptosis, pyroptosis, ferroptosis and NETosis, can also contribute to DAMP release. In addition, some DAMPs can be exported actively from live cells by exocytosis of secretory lysosomes or exosomes, ectosomes, and activation of cell membrane channel pores. Here we review the shared and DAMP-specific mechanisms reported in the literature for high mobility group box 1, ATP, extracellular cold-inducible RNA-binding protein, histones, heat shock proteins, extracellular RNAs and cell-free DNA.

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Section: Universal Mechanisms Of Damp Releasementioning

confidence: 99%

Release mechanisms of major DAMPs

et al. 2021

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“…Gemcitabine, used to treat breast cancer recurrence, induces the release of characteristic immunostimulatory DAMPs, such as HMGB1, CRT, and HSP70, in bladder cancer cells, but does not cause ICD of these cells [ 105 ]. The release of prostaglandin E 2 inhibits the immunostimulatory effects of DAMPs, and prostaglandin E 2 blockade activates DCs, followed by the priming of antitumor immune responses by CD8+ T cells, leading to tumor rejection and the failure to induce ICD [ 105 ]. These findings suggest that the balance between immunostimulatory and inhibitory DAMPs determines the induction of ICD by anticancer agents.…”

Section: Exploiting the Double-edged Sword Of Damps For Antitumor Immunitymentioning

confidence: 99%

Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer

Kim¹,

Kin

2021

Cancers

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How primary breast cancer can be cured after (neo)adjuvant therapy remains unclear at the molecular level. Immune activation by anticancer agents may contribute to residual tumor cell eradication with postsurgical (neo)adjuvant chemotherapy. Chemotherapy-induced immunogenic cell death (ICD) may result in long-term immune activation with memory effector T cells, leading to a primary breast cancer cure. Anthracycline and taxane treatments cause ICD and immunogenic modulations, resulting in the activation of antitumor immunity through damage-associated molecular patterns (DAMPs), such as adenosine triphosphate, calreticulin, high mobility group box 1, heat shock proteins 70/90, and annexin A1. This response may eradicate residual tumor cells after surgical treatment. Although DAMP release is also implicated in tumor progression, metastasis, and drug resistance, thereby representing a double-edged sword, robust immune activation by anticancer agents and the subsequent acquisition of long-term antitumor immune memory can be essential components of the primary breast cancer cure. This review discusses the molecular mechanisms by which anticancer drugs induce ICD and immunogenic modifications for antitumor immunity and targeted anti-DAMP therapy. Our aim was to improve the understanding of how to eradicate residual tumor cells treated with anticancer drugs and cure primary breast cancer by enhancing antitumor immunity with immune checkpoint inhibitors and vaccines.

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“…Photon Upconversion and therapeutic effect of in vitro of UCMS@Pep ", UCMS@Pep-RB with NIR laser could promote apoptosis and necrosis of LLC cells. Apoptotic or necrotic cancer cells can express or release DAMPs that generate an “eat me” signal to elicit immune system, recruit immune cells [ 31 ], and subsequently promote ICD, which have a central effect in immunotherapy [ 32 , 33 ]. CRT, HMGB1, and ATP are noted as key DAMPs [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal

Wang

Chen

et al. 2021

J Nanobiotechnol

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The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.

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Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death

Cited by 180 publications

References 71 publications

Release mechanisms of major DAMPs

Release mechanisms of major DAMPs

Current and Future Therapies for Immunogenic Cell Death and Related Molecules to Potentially Cure Primary Breast Cancer

Peptide vaccine-conjugated mesoporous carriers synergize with immunogenic cell death and PD-L1 blockade for amplified immunotherapy of metastatic spinal

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