Costimulation of Effector CD8+ T Cells: Which Receptor is Optimal for Immunotherapy?

Abstract

To induce strong immune responses, naive CD8 + T cells require stimulation through the TCR and costimulatory receptors. However, the biological consequence of activating costimulatory receptors on effector T cells is still unclear. In addition, activating CD8 + T cells either with vaccination or adoptive transfer of activated or gene-modified T cells are novel approaches for cancer and antiviral therapies. To enhance T cell efficacy, activation of costimulatory receptors is often incorporated in therapeutic designs; however it is still unclear how stimulation of different costimulatory receptors influences T cell function. Therefore it is essential to study how different costimulation receptors alter the gene expression and functions of activated CD8+ T cells. This will determine how combinations of costimulatory signals shape immunity and how to best activate and utilize these receptors for immunotherapy.

The landscape of novel and complementary targets for immunotherapy: an analysis of gene expression in the tumor microenvironment

“…As a purely correlation-based approach, our exome-wide expression analysis is very coarse-grained, and does not incorporate multi-omic pharmacogenomic data [54] or the specific molecular biology of the genes identified. Extensive molecular biological research on their functional and structural properties is required to assess their viability as immunomodulatory targets [55, 56]. However, the guidance provided by our approach complements extant molecular biological investigation, highlighting well-studied genes that deserve continued attention as well as pointing out genes whose molecular biology is less well known, but which could be important for future research.…”

Deconvolving clinically relevant cellular immune crosstalk from bulk gene expression using CODEFACS and LIRICS

“…4B, Fig. 3A interactions improve anti-tumor immune responses even in low TMB and highly immunosuppressive settings [32][33][34][35][36][37] . Currently, several clinical trials to assess the safety and efficacy of these combinations are in progress [38][39][40][41] .…”

Widespread genomic de novo DNA methylation occurs following CD8 + T cell activation and proliferation

“…Upon antigen recognition and co-stimulation, intracellular signalling pathways are activated within the CD8+ T cell. This leads to the production of various cytokines and the upregulation of cell surface molecules involved in effector function [ 7 ]. Activated CD8+ T cells undergo clonal expansion, where a small number of antigen-specific T cells rapidly proliferate into a large population of effector cells.…”