Tumor interferon signaling regulates a multigenic resistance program
Inhibiting immune checkpoints can lead to immune resistance and tumor escape. Prolonged interferon signaling was found to foster STAT1-mediated, PD-L1–independent resistance through IFN-driven inhibitory ligands. Blocking tumor IFN signaling expanded and renewed distinct exhausted TILs and regained effectiveness of single-checkpoint blockade.
Mass spectrometry profiling of HLA-associated peptidomes in mono-allelic cells enables more accurate epitope prediction
Cells express multiple HLA proteins, making elution and identification of the peptidome for any one arduous. However, by expressing only one HLA molecule on the cell at a time, identifying peptides with optimized LS-MS/MS, and using neural networks, algorithms were developed that appear to more accurately identify dominant and subdominant motifs for multiple HLA alleles.
A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes
A hallmark of pDCs has been their strong production of type I interferons. A phenotypically distinct subset of pDCs was found that produces no IFN, but rather effectively activates B cells to produce antibodies, stimulates CD4+ T cells to proliferate, and promotes Treg formation.
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
CAR T cells have provided patients with remissions from B-cell cancers, but can become exhausted. CRISPR/Cas-9 was used to slip a CAR directly into the TCRα constant locus, enabling T cells to express it uniformly, internalize it after engagement, and then re-express it post antigen exposure, delaying exhaustion.
MHC class I–associated peptides derive from selective regions of the human genome
An extensive analysis of 27 HLA-A and –B allotypes found their bound peptides derive from only 60% of expressed genes in B-LCLs and comprise only 10% of the total sequences expressed. This perhaps explains why the hit-rate from binding predictions for neoepitopes is low—few mutations may reside in peptide-generating regions of the exome.
CD8+ T cells orchestrate pDC-XCR1+ dendritic cell spatial and functional cooperativity to optimize priming
For an efficient T cell response, various immune cells must cooperate. CD8 cells engaging their ligand were found to orchestrate their own optimal local environment through production of chemokines that attract the appropriate dendritic cell subsets to the right location in a multistep, multicellular process that promotes DC maturation and enhances cross-presentation.