- Title
- Innate-like T cells in patients with cancer
- Creator
- Minoda, Yosuke
- Date
- 2017
- Type
- Text; Thesis; PhD
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/166481
- Identifier
- vital:13449
- Identifier
- https://library.federation.edu.au/record=b2752392
- Abstract
- Innate-like T cells, including invariant natural killer T (NKT), mucosal associated invariant T (MAIT) cells or g T cells are associated with regulation of anti-tumour responses in humans and mice, although their exact role remains controversial. We have studied innate-like T cells from tumour infiltrating lymphocytes (TILS), peripheral blood mononuclear cells (PBMCs) and bone marrow (BM) derived cells from patients undergoing treatment for cancer and compared their characteristics to cells from healthy donors. We identifed that the overall frequency of innate-like T cells was variably deficient in patients with blood or solid cancers. Interestingly, the deficiency of innate-like T cells appeared to be more severe than that of other T cells suggesting a specific impact. An increased proportion of activated g T cells and MAIT cells suggested they could have a functional role in responses to cancer cells. Despite the deficiency of these subsets in patient tissue samples, we showed that anti-tumour capacity of innate-like T cells was intact as innate-like T cells in most patient groups had a similar cytokine response to stimulation as cells from healthy donors. Finally, we also showed that innate-like T cells appeared not to broadly recognize cancer cells, as no direct impact was identified in their overall frequency or cytokine expression when exposed to autologous tumour cells, cancer lysates or lipids extracted from patient tumours, or colorectal cancer cell lines. This project was aimed at providing an overview of potential defects in innate-like T cells based on my analysis of a wide range of samples in the Fiona Elsey Cancer Research Institute (FECRI) Tissue Bank. As a result of my studies, we have established a clear understanding of innate cells in cancer, which provides a basis for future studies. Our novel findings include analysis of frequency distribution and functional capacity of MAIT cells in solid tumours other than colorectal cancer and in patients with blood cancers such as chronic lymphocytic leukaemia (CLL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) or other haematological malignancies, something not previously reported. Taken together, we showed that a deficiency of innate-like T cells is common in patient groups with cancer and could be a risk factor for disease and possibly a target for immunotherapies, but the functional capacity was intact for cytokine responses.; Doctor of Philosophy
- Publisher
- Federation University Australia
- Rights
- Copyright Yosuke Minoda
- Rights
- Open Access
- Rights
- This metadata is freely available under a CCO license
- Subject
- Innate-like T cells; Cancer; Tumour
- Full Text
- Thesis Supervisor
- Berzins, Stuart
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