Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell–driven tumor immunity

Andrade, Lucas Ferrari de; Tay, Rong En; Pan, Deng; Luoma, Adrienne; Ito, Yoshinaga; Badrinath, S; Tsoucas, Daphne; Franz, Bettina; May, Kenneth F.; Harvey, Christopher J.; Kobold, Sebastian; Pyrdol, Jason W.; Yoon, Charles H.; Yuan, Guo‐Cheng; Hodi, F. Stephen; Dranoff, Glenn; Wucherpfennig, Kai W.

doi:10.1126/science.aao0505

Cited by 321 publications

(275 citation statements)

References 40 publications

(45 reference statements)

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“…NK cell-driven antitumor immunotherapy has been successfully demonstrated to treat melanoma by inhibiting MICA/B shedding in a humanized mouse model. 30 Therefore, immunotherapeutic assessment of lomofungin in vivo is warranted in future studies since chemotherapeutic effects of ADAM17 silencing against HCC have been proved. 31 In conclusion, lomofungin can be an attractive agent for the immunological control of HCC, via the suppression of the new target, ADAM17.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells

Arai

Goto

Tanoue

et al. 2018

Intl Journal of Cancer

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In our previous study on hepatocellular carcinoma (HCC) susceptibility genes in chronic hepatitis patients, we identified the MHC class I polypeptide-related sequence A (MICA). Natural killer cells eliminate various cancer cells, including HCC, by suppressing MICA shedding. Therefore, we investigated MICA sheddases and inhibitors for HCC immunotherapy. In this study, HepG2, PLC/PRF/5, and Hep3B were treated with the siRNA of a disintegrin and metalloproteases (ADAMs) and matrix metalloproteases to measure the concentration of soluble MICA (sMICA) by ELISA to detect the therapeutic target. Furthermore, an FDA-approved drug library was tested for the enzymatic inhibition of the targeted enzyme in an in vitro drug screening assay system. ADAM17 knockdown reduced sMICA levels and increased membrane-bound MICA (mMICA) expression in HCC cells. In an in vitro drug screen using an FDA-approved drug library, lomofungin, an antifungal drug, was found to strongly decrease ADAM17 activity. In HCC cells, mMICA expression was induced and sMICA production was inhibited in a dose-dependent manner. These effects were cancelled upon ADAM17 knockdown, suggesting that lomofungin targeted ADAM17. Analysis of lomofungin analogs revealed the responsible functional groups. In summary, we suggest lomofungin to be an attractive agent for the immunological control of HCC, via the suppression of ADAM17.

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Section: Discussionmentioning

confidence: 99%

Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells

Arai

Goto

Tanoue

et al. 2018

Intl Journal of Cancer

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“…[126][127][128][129][130][131] However, NK cell-based cancer therapy was not widely explored, as most cancer cells express selfmarkers. [126][127][128][129][130][131] However, NK cell-based cancer therapy was not widely explored, as most cancer cells express selfmarkers.…”

Section: Strategy To Potentiate Nk Cellsmentioning

confidence: 99%

Nanomedicine‐Based Immunotherapy for the Treatment of Cancer Metastasis

et al. 2019

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Metastasis is the leading cause of cancer‐associated death, with poor prognosis even after extensive treatment. The dormancy of metastatic cancer cells during dissemination or after colony formation is one major reason for treatment failure, as most drugs target cells of active proliferation. Immunotherapy has shown great potential in cancer therapy because the activity of effector cells is less affected by the metabolic status of cancer cells. In addition, metastatic cells out of immunosuppressive tumor microenvironment (TME) are more susceptible to immune clearance, although these cells can achieve immune surveillance evasion via strategies such as platelet and macrophage recruitment. Since nanomaterials themselves or their carried drugs have the capability to modulate the immune system, a great amount of focus has been placed on nanomedicine strategies that leverage immune cells participating the metastatic cascade. These nanomedicines successfully inhibit the tumor metastasis and prolong the survival of model animals. Immune cells that are involved in the metastasis cascade are first summarized and then recent and inspiring strategies and nanomaterials in this growing field are highlighted.

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“…) . Strategies aimed at targeting metalloproteases or that encompass antibody‐mediated blocking of MICA ligand release in conjunction with chemotherapy could be successful to preserve NKG2D ligands on the cell surface of senescent cells …”

Section: Nk Cell‐mediated Clearance Of Senescent Tumor Cellsmentioning

confidence: 99%

Senescent cells: Living or dying is a matter of NK cells

Antonangeli

Zingoni

Soriani

et al. 2019

Journal of Leukocyte Biology

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NK cells are lymphocytes of the innate immune system, which are able to deal promptly with stressed cells. Cellular senescence is a cell stress response leading to cell cycle arrest that plays a key role during tissue homeostasis and carcinogenesis. In this review, how senescent cells trigger an immune response and, in particular, the ability of NK cells to recognize and clear senescent cells are discussed. Special attention is given to the NK cell‐mediated clearance of senescent tumor cells. NK cells kill senescent cells through a mechanism involving perforin‐ and granzyme‐containing granule exocytosis, and produce IFN‐γ following senescent cell interaction, leading to hypothesize that NK cell‐mediated immune clearance of senescent cells not only relies on direct killing but also on cytokine production, that in turn can promote macrophage activation. These aspects, as well as the ability of the senescence‐associated secretory phenotype and senescent cell‐produced extracellular vesicles to modulate NK cell effector functions, are described.

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Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell–driven tumor immunity

Cited by 321 publications

References 40 publications

Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells

Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells

Nanomedicine‐Based Immunotherapy for the Treatment of Cancer Metastasis

Senescent cells: Living or dying is a matter of NK cells

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