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.
Highlights
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Internal proteins are broken up by proteasomes to form peptides that are transported by transporter associated with antigen processing (TAP) to major histocompatibility (MHC) I molecules in the lumen of the endoplasmic reticulum
The peptide–MHC I complexes generated via these antigen processing and presentation pathways can be recognized by T cell receptors (TCRs) on Cytotoxic T lymphocytes (CTLs)
Summary
As a part of the body’s immunosurveillance mechanism, all nucleated cells display major histocompatibility (MHC) class I molecules, enabling the routine presentation of cellular peptide fragments on their plasma membrane. An abundance of suppressive immune cells, including regulatory T cells (Tregs), myeloid-derived suppressor cells, and tumour-associated macrophages, infiltrate into the tumour and deliver a host of negative signals to tumourspecific T cells and antigen-presenting cells including dendritic cells. As these features of the tumour microenvironment have been reviewed extensively elsewhere (see Refs [6,7,8,9,10,11]), we will focus here on an examination of alterations to antigen processing and presentation. Imal studies [19H,2e4n,2c5e],. iHt iesnicme,piotritsanimt tpoocratarneftutlolycdareefifnuellythdeemfinoeletchuelamr molechualanrismmeschreas-ponsible for a nisms responsibplearftoicrualapraarlttiecrualtaiornalitnerMatHioCnIinphMenHoCtypI ephperinoorttyopdeepsirgionrintgo sdpeesciigfincinwgaysps eto- restore in situ cific ways to restuomreoiunrsMituHtCumI eoxuprrMessHioCn.I expression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
