Lizeth Meza - Inflammation division

Lizeth Meza - Inflammation division

Location: 
Online
Start Time: 
Mon, 11/10/2021 - 3:00pm
End Time: 
Mon, 11/10/2021 - 4:00pm

WEHI PhD Completion Seminar hosted by Associate Professor Sandra Nicholson

 

Lizeth Meza Guzman

PhD Student - Nicholson Laboratory

Inflammation division - Infection, Inflammation & Immunity Theme

 

The Natural Killer (Cells) Within

 

Join via TEAMS

Including Q&A session

 

Natural Killer (NK) cell-mediated immunotherapy is now an established milestone in the development of new cancer therapies, gaining traction due to the intrinsic ability of the NK cell to target and kill tumour cells. However, to fully harness the tumour killing ability of NK cells we still need to overcome hurdles such as limited NK cell infiltration in solid tumours, the up- or down-regulation of inhibitory or activating NK cell receptors or ligands, and the compromised cytotoxicity of adoptively transferred NK cells in a suppressive tumour microenvironment (TME). During my PhD, I focused on two candidate proteins for immune checkpoint blockade in NK cells: the receptor-like protein tyrosine phosphatase CD45 and the E3 ubiquitin ligase Cbl-b.

 

Previous studies had shown that CD45 deficient mice exhibit increased numbers of NK cells, while NK cells which either lack Cbl-b or express an “E3 ligase-defective” Cbl-b, display prolonged NK activation and enhanced control of B16F10 melanoma tumour cells in vivo (Huntington, Xu et al. 2005, Paolino, Choidas et al. 2014). These defining characteristics in mouse models suggested that therapeutic blockade of either CD45 or Cbl-b might overcome some of the current limitations of NK cell therapies. To explore this potential, I investigated the mechanism underlying the enhanced NK cell numbers in CD45 deficient mice, demonstrating that this occurs, at least in part, due to an early defect in lymphoid progenitors and skewing towards a mature cytotoxic NK cell. I also identified several key activating NK receptors that are negatively regulated by Cbl-b. The therapeutic potential of these findings will be discussed.

 

Lizeth Meza Guzman received her MSc in Plant biotechnology in 2016, from the Wageningen University & Research (WUR) in The Netherlands. In 2018, she was recruited under the WEHI International PhD Scholar Initiative to the Huntington laboratory in the Immunology division.

 

Huntington, N. D., Y. Xu, S. L. Nutt and D. M. Tarlinton (2005). "A requirement for CD45 distinguishes Ly49D-mediated cytokine and chemokine production from killing in primary natural killer cells." J Exp Med 201(9): 1421-1433.

Paolino, M., A. Choidas, S. Wallner, B. Pranjic, I. Uribesalgo, S. Loeser, A. M. Jamieson, W. Y. Langdon, F. Ikeda, J. P. Fededa, S. J. Cronin, R. Nitsch, C. Schultz-Fademrecht, J. Eickhoff, S. Menninger, A. Unger, R. Torka, T. Gruber, R. Hinterleitner, G. Baier, D. Wolf, A. Ullrich, B. M. Klebl and J. M. Penninger (2014). "The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells." Nature 507(7493): 508-512.

 

All welcome!