Enhancing CD8+ T Cell Fatty Acid Catabolism within a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy
September 27, 2017
We know that when oxygen is lacking, T cells increase their glucose uptake and glycolysis, and when glucose is lacking, cells switch to oxidative phosphorylation (OXPHOS), which can utilize many substrates for fuel, but requires oxygen. But what happens to the T cells in the tumor microenvironment (TME), which is often hypoxic and...
The inhibitory signaling receptor protocadherin-18 regulates tumor-infiltrating CD8+ T cell function
September 20, 2017
The activation of T cells from a memory to an effector state depends on the integration of the positive signal from the T cell receptor upon binding with a cognate antigen and the negative signals from any of several inhibitory signaling receptors (ISRs) binding their cognate ligands on the antigenic cell’s surface. ISRs...
The Effect of Timing is Crucial in PD-1 Blockade/Agonist-OX40 Combination Immunotherapy
September 13, 2017
Timing is everything, especially when it comes to combination immunotherapy. This was the conclusion reached by two separate research groups that evaluated the combination of agonist-OX40 and anti-PD-1 antibody therapies in different mouse models. The researchers were inspired by the challenges of optimally combining immunotherapies in the clinical setting. To address this problem...
PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity
September 6, 2017
PD-L1 is doubling down on defense. It is well-known that cancer cells often upregulate PD-L1 as a mode of defense against the immune system, however, this new research by Gato-Cañas et al. suggests that PD-L1 may also play a direct defensive role within the tumor cell by conferring resistance to IFN-mediated cytotoxicity and...