Weekly Digests

2017

August

Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade

August 30, 2017

As the role of anti-PD-1 and anti-CTLA-4 immune checkpoint blockades (ICB) in cancer therapy continues to expand, understanding the underlying mechanisms of action becomes more imperative. Based on temporal, spatial, and cellular source differences, Wei et al. hypothesized that the anti-tumor immune responses to anti-CTLA-4 and anti-PD-1 treatment are driven by distinct mechanisms...

Constitutive IDO1 Expression in Human Tumors is Driven by Cyclooxygenase-2 and Mediates Intrinsic Immune Resistance

August 23, 2017

Cancers are the escape artists of the biological world, each with a unique act by which it eludes or overpowers the immune system of an affected organism. Some human cancers have been found to constitutively express indoleamine 2,3-dioxygenase 1 (IDO1), which rapidly catabolizes tryptophan to kynurenine, creating an immunosuppressive microenvironment that prevents T...

Multi-level Strategy for Identifying Proteasome-Catalyzed Spliced Epitopes Targeted by CD8+ T Cells during Bacterial Infection

August 16, 2017

It is well known that enzymes catalyze reactions in both directions, and so the ability of proteasomes to not only cleave larger peptides into smaller ones but also splice smaller peptides into larger ones should not be surprising; however, the biological data demonstrating this has been limited. Platteel et al. describe a multi-level...

TCR repertoire intratumor heterogeneity in localized lung adenocarcinomas: an association with predicted neoantigen heterogeneity and postsurgical recurrence

August 9, 2017

Large tumors can be difficult to address not only due to their size, but also their internal complexity and heterogeneity. Building on their previous work, in which whole exome sequencing of 2-5 spatially different regions from resected localized lung adenocarcinomas from 11 patients revealed that mutational genomic intratumor heterogeneity (ITH) was linked to...

Specificity of inhibitory KIRs enables NK cells to detect changes in an altered peptide environment

August 2, 2017

The simple hypothesis that NK cells discriminate “self” from “non-self” based on surface HLA expression understates the complexity of NK cell recognition, and now needs to be extended to include discrimination of “altered self”. As the recent study by Carrillo-Bustamante et al. suggests, changes in the peptide-ligand repertoire appear to play a role...