ORCID Profile
0000-0003-0524-0444
Current Organisation
The Walter and Eliza Hall Institute
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Publisher: Elsevier BV
Date: 05-2023
Publisher: Elsevier BV
Date: 10-2020
DOI: 10.1016/J.IMMUNI.2020.09.010
Abstract: The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes anti-tumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8
Publisher: Portland Press Ltd.
Date: 12-2022
DOI: 10.1042/BSR20221683
Abstract: Suppressor of cytokine signaling (SOCS) 2 is the critical negative regulator of growth hormone (GH) and prolactin signaling. Mice lacking SOCS2 display gigantism with increased body weight and length, and an enhanced response to GH treatment. Here, we characterized mice carrying a germ-line R96C mutation within the SOCS2-SH2 domain, which disrupts the ability of SOCS2 to interact with tyrosine-phosphorylated targets. Socs2R96C/R96C mice displayed a similar increase in growth as previously observed in SOCS2 null (Socs2−/−) mice, with a proportional increase in body and organ weight, and bone length. Embryonic fibroblasts isolated from Socs2R96C/R96C and Socs2−/− mice also showed a comparable increase in phosphorylation of STAT5 following GH stimulation, indicating the critical role of phosphotyrosine binding in SOCS2 function.
Publisher: Wiley
Date: 19-10-2023
DOI: 10.1111/IMCB.12701
Publisher: Elsevier BV
Date: 07-2022
Publisher: Cold Spring Harbor Laboratory
Date: 17-04-2023
DOI: 10.1101/2023.04.17.537109
Abstract: The clinical development of Natural Killer (NK) cell-mediated immunotherapy marks a milestone in the development of new cancer therapies and has gained traction due to the intrinsic ability of the NK cell to target and kill tumour cells. To fully harness the tumour killing ability of NK cells, we need to improve NK cell persistence and overcome suppression of NK cell activation in the tumour microenvironment. The trans-membrane, protein tyrosine phosphatase CD45, regulates NK cell homeostasis, with genetic loss of CD45 in mice resulting in increased numbers of mature NK cells [1–3]. This suggests that CD45-deficient NK cells might display enhanced persistence following adoptive transfer. However, here we demonstrated that adoptive transfer of CD45-deficiency did not enhance NK cell persistence in mice, and instead, the homeostatic disturbance of NK cells in CD45-deficient mice stemmed from a developmental defect in the common lymphoid progenitor population. The enhanced maturation within the CD45-deficient NK cell compartment was intrinsic to the NK cell lineage, and independent of the developmental defect. CD45 is not a conventional immune checkpoint candidate, as systemic loss is detrimental to T and B cell development [4–6], compromising the adaptive immune system. Nonetheless, this study suggests that inhibition of CD45 in progenitor or stem cell populations may improve the yield of in vitro generated NK cells for adoptive therapy.
Publisher: MDPI AG
Date: 11-04-2020
Abstract: Natural killer (NK) cells play a pivotal role in cancer immunotherapy due to their innate ability to detect and kill tumorigenic cells. The decision to kill is determined by the expression of a myriad of activating and inhibitory receptors on the NK cell surface. Cell-to-cell engagement results in either self-tolerance or a cytotoxic response, governed by a fine balance between the signaling cascades downstream of the activating and inhibitory receptors. To evade a cytotoxic immune response, tumor cells can modulate the surface expression of receptor ligands and additionally, alter the conditions in the tumor microenvironment (TME), tilting the scales toward a suppressed cytotoxic NK response. To fully harness the killing power of NK cells for clinical benefit, we need to understand what defines the threshold for activation and what is required to break tolerance. This review will focus on the intracellular signaling pathways activated or suppressed in NK cells and the roles signaling intermediates play during an NK cytotoxic response.
Publisher: Springer US
Date: 2022
DOI: 10.1007/978-1-0716-2160-8_13
Abstract: Stimulation of Natural Killer (NK) cells with cytokines, target cell interaction, or antibody mediated activation of receptors on the NK cell surface enables the dissection of specific signaling intermediates in different activation pathways. NK cell activation status is commonly measured by production of interferon gamma (IFNγ) and expression of the degranulation marker LAMP-1 (CD107a). Cytotoxic potency can also be assessed by the production of perforin, granzymes, and tumor necrosis factor alpha (TNFα). NK cell receptor mediated activation by antibodies requires crosslinking of the receptor-specific antibodies thus, in vitro activation assays are performed by binding antibodies to cell culture plates. All parameters can be measured by flow cytometry.
Location: Australia
No related grants have been discovered for Lizeth Meza Guzman.