The lectin Siglec-G inhibits dendritic cell cross-presentation by impairing MHC class I–peptide complex formation
Cross-presentation of tumor antigens is key to the activation of T cells by dendritic cells. Siglec-G was found to interfere with peptide–MHC class I complex formation through inhibition of NOX2-mediated phagosome alkalinization, a condition conducive to optimal peptide loading.
Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer
The Keynote-024 trial was designed to compare the mAb pembrolizumab with chemotherapies as first-line treatments for NSCLC. Patients, preselected to have >50% PD-L1+ tumors, survived longer and with fewer serious adverse effects with pembrolizumab than chemotherapy.
Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy
Image: Photo by David Dixon http://www.geograph.org.uk/photo/3492475
Melanomas responsive to anti–CTLA-4 blockade are sensitive to IFNγ. IFNGR1-knockdown tumors in mice, and tumors from nonresponder patients, jump this hurdle by deleting or accumulating mutations in their IFNγ response pathways, which promotes tumor survival despite CTLA-4 blockade. This may represent a common mechanism for resistance to checkpoint blockade therapy.
Nivolumab for recurrent squamous-cell carcinoma of the head and neck
Patients with HNSCC with tumors resistant to standard platinum-based treatment were randomized to receive anti-PD-1 (nivolumab) or another standard therapy. Nivolumab significantly prolonged survival, PD-L1 status notwithstanding, compared with standard therapies, and patients experienced fewer serious adverse effects.
A large fraction of HLA class I ligands are proteasome-generated spliced peptides
The proteasome cleaves proteins into peptides presented by class I on the cell surface. About a third of the HLA peptidome was found to consist of spliced-together peptides, creating new epitopes and a mechanism for presenting a broader spectrum of epitopes relevant to immunobiology and autoimmunity that are not accounted for in current prediction algorithms.
Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia
NK memory cells were tested as antitumor therapeutics in vitro and in vivo in a xenografted mouse model. These cells were effective cancer cell killers and also proved safe and promisingly effective in a small phase I clinical trial.
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