granzymes

Summary

Summary: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.

Top Publications

  1. Graubert T, Russell J, Ley T. The role of granzyme B in murine models of acute graft-versus-host disease and graft rejection. Blood. 1996;87:1232-7 pubmed
    ..These in vivo data define significant role for gzm B in cytotoxicity mediated by CD8+ CTL, but not by CD4+ CTL. Furthermore, these results do not support a model of hybrid resistance in which NK cells play a pivotal role. ..
  2. Jiang Y, Yang M, Sun X, Chen X, Ma M, Yin X, et al. IL-10+ NK and TGF-β+ NK cells play negative regulatory roles in HIV infection. BMC Infect Dis. 2018;18:80 pubmed publisher
  3. Tzannou I, Nicholas S, Lulla P, Aguayo Hiraldo P, Misra A, Martinez C, et al. Immunologic Profiling of Human Metapneumovirus for the Development of Targeted Immunotherapy. J Infect Dis. 2017;216:678-687 pubmed publisher
    ..Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections. ..
  4. Kuo L, Cheng L, Lee C, Lin C, Chen P, Li L. Estrogen and cigarette sidestream smoke particulate matter exhibit ER?-dependent tumor-promoting effects in lung adenocarcinoma cells. Am J Physiol Lung Cell Mol Physiol. 2017;313:L477-L490 pubmed publisher
    ..This study demonstrates that estrogen has ER?-dependent tumor-promoting activity. CSSP acts like estrogen and shows a potential to enhance estrogen-induced ER? action. ..
  5. Meng F, Zhen S, Song B. HBV-specific CD4+ cytotoxic T cells in hepatocellular carcinoma are less cytolytic toward tumor cells and suppress CD8+ T cell-mediated antitumor immunity. APMIS. 2017;125:743-751 pubmed publisher
  6. Wong H, Cvijanovich N, Anas N, Allen G, Thomas N, Bigham M, et al. Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP. Am J Respir Crit Care Med. 2017;196:494-501 pubmed publisher
    ..PERSEVERE-XP significantly improves on PERSEVERE and suggests a role for TP53-related cellular division, repair, and metabolism in the pathophysiology of septic shock. ..
  7. Lin R, Chen L, Chen G, Hu C, Jiang S, Sevilla J, et al. Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression. J Clin Invest. 2014;124:5352-67 pubmed publisher
    ..Together, our findings provide a miRNA-based strategy that subverts the immunosuppression of CTLs that is often observed during adoptive cell transfer tumor immunotherapy and identify a TGF-β-mediated tumor immune-evasion pathway. ..
  8. Ribeiro A, Laranjeira P, Mendes S, Velada I, Leite C, Andrade P, et al. Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther. 2013;4:125 pubmed publisher
    ..Despite the similarities between the three types of MSCs evaluated, we detect important differences that should be taken into account when choosing the MSC source for research or therapeutic purposes. ..
  9. Zhu L, Aly M, Wang H, Karakizlis H, Weimer R, Morath C, et al. Decreased NK cell immunity in kidney transplant recipients late post-transplant and increased NK-cell immunity in patients with recurrent miscarriage. PLoS ONE. 2017;12:e0186349 pubmed publisher

More Information

Publications25

  1. Klein Hessling S, Muhammad K, Klein M, Pusch T, Rudolf R, Flöter J, et al. NFATc1 controls the cytotoxicity of CD8+ T cells. Nat Commun. 2017;8:511 pubmed publisher
    ..Here the authors show NFATc1 controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells. ..
  2. de Jong H, García Laorden M, Hoogendijk A, Parry C, Maude R, Dondorp A, et al. Expression of intra- and extracellular granzymes in patients with typhoid fever. PLoS Negl Trop Dis. 2017;11:e0005823 pubmed publisher
    ..enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the ..
  3. Pallett L, Davies J, Colbeck E, Robertson F, Hansi N, Easom N, et al. IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection. J Exp Med. 2017;214:1567-1580 pubmed publisher
    ..We suggest that these inhibitory molecules, together with paradoxically robust, rapid, cell-autonomous IL-2 and IFNγ production, equip liver CD8 TRM to survive while exerting local noncytolytic hepatic immunosurveillance. ..
  4. Heibein J, Goping I, Barry M, Pinkoski M, Shore G, Green D, et al. Granzyme B-mediated cytochrome c release is regulated by the Bcl-2 family members bid and Bax. J Exp Med. 2000;192:1391-402 pubmed
    ..Our results provide evidence for a new pathway by which CTLs inflict damage and explain the caspase-independent mechanism of mitochondrial dysfunction. ..
  5. Pellegatta S, Valletta L, Corbetta C, Patanè M, Zucca I, Riccardi Sirtori F, et al. Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma. Acta Neuropathol Commun. 2015;3:4 pubmed publisher
    ..These results support the translational potential of immunotherapeutic targeting of gliomas carrying IDH1 mutations. ..
  6. Klose D, Woitok M, Niesen J, Beerli R, Grawunder U, Fischer R, et al. Generation of an artificial human B cell line test system using Transpo-mAbTM technology to evaluate the therapeutic efficacy of novel antigen-specific fusion proteins. PLoS ONE. 2017;12:e0180305 pubmed publisher
    ..Our data confirm that antigen-based fusion proteins containing granzyme B (R201K) are suitable candidates for the depletion of autoreactive B cells. ..
  7. Thabet N, Moustafa E. Synergistic effect of Ebselen and gamma radiation on breast cancer cells. Int J Radiat Biol. 2017;93:784-792 pubmed publisher
  8. Xing J, Zhang C, Yang X, Wang S, Wang Z, Li X, et al. CXCR5+CD8+ T cells infiltrate the colorectal tumors and nearby lymph nodes, and are associated with enhanced IgG response in B cells. Exp Cell Res. 2017;356:57-63 pubmed publisher
  9. Voskoboinik I, Whisstock J, Trapani J. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15:388-400 pubmed
    ..and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, ..
  10. Serafini B, Scorsi E, Rosicarelli B, Rigau V, Thouvenot E, Aloisi F. Massive intracerebral Epstein-Barr virus reactivation in lethal multiple sclerosis relapse after natalizumab withdrawal. J Neuroimmunol. 2017;307:14-17 pubmed publisher
    ..These results may encourage switching to B-cell depleting therapy after natalizumab discontinuation. ..
  11. Colaert N, Helsens K, Martens L, Vandekerckhove J, Gevaert K. Improved visualization of protein consensus sequences by iceLogo. Nat Methods. 2009;6:786-7 pubmed publisher
  12. Yin W, Song Y, Liu Q, Wu Y, He R. Topical treatment of all-trans retinoic acid inhibits murine melanoma partly by promoting CD8+ T-cell immunity. Immunology. 2017;152:287-297 pubmed publisher
    ..Hence, our study demonstrates that topical atRA treatment effectively inhibits melanoma growth partly by promoting the differentiation and the cytotoxic function of effector CD8+ T cells. ..
  13. Kah J, Koh S, Volz T, Ceccarello E, Allweiss L, Lutgehetmann M, et al. Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection. J Clin Invest. 2017;127:3177-3188 pubmed publisher
    ..T cell transfer did not trigger inflammation in uninfected mice. These data support the feasibility of using mRNA electroporation to engineer HBV TCR-redirected T cells in patients with chronic HBV infection. ..
  14. Larimer B, Wehrenberg Klee E, Dubois F, Mehta A, Kalomeris T, Flaherty K, et al. Granzyme B PET Imaging as a Predictive Biomarker of Immunotherapy Response. Cancer Res. 2017;77:2318-2327 pubmed publisher
    ..Overall, our results suggest granzyme B PET imaging can serve as a quantitatively useful predictive biomarker for efficacious responses to cancer immunotherapy. Cancer Res; 77(9); 2318-27. ©2017 AACR. ..
  15. Nagler A, Lanier L, Cwirla S, Phillips J. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989;143:3183-91 pubmed
    ..Based on these results, we propose that these NK cell subsets represent portions of the NK cell differentiation pathway present in the peripheral blood. ..
  16. Wagner L, Yang O, Garcia Zepeda E, Ge Y, Kalams S, Walker B, et al. Beta-chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans. Nature. 1998;391:908-11 pubmed
    ..This association appears to have a functional significance, because heparan sulphate facilitates RANTES inhibition of HIV-1 infection of monocytes. ..