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Investigating T Cell Immunity in Cancer: Achievements and Prospects
Authors:Zhen Zeng  Hui Yi Chew  Jazmina G Cruz  Graham R Leggatt  James W Wells
Affiliation:Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; (Z.Z.); (H.Y.C.); (J.G.C.); (G.R.L.)
Abstract:T cells play a key role in tumour surveillance, both identifying and eliminating transformed cells. However, as tumours become established they form their own suppressive microenvironments capable of shutting down T cell function, and allowing tumours to persist and grow. To further understand the tumour microenvironment, including the interplay between different immune cells and their role in anti-tumour immune responses, a number of studies from mouse models to clinical trials have been performed. In this review, we examine mechanisms utilized by tumour cells to reduce their visibility to CD8+ Cytotoxic T lymphocytes (CTL), as well as therapeutic strategies trialled to overcome these tumour-evasion mechanisms. Next, we summarize recent advances in approaches to enhance CAR T cell activity and persistence over the past 10 years, including bispecific CAR T cell design and early evidence of efficacy. Lastly, we examine mechanisms of T cell infiltration and tumour regression, and discuss the strengths and weaknesses of different strategies to investigate T cell function in murine tumour models.
Keywords:CD8 T cells  cytotoxic T lymphocytes  cancer  immunotherapy  CAR  tumour antigen  checkpoint inhibitor
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