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Image: Dendritic cells from Broz ML & Krummel MF. Cancer Immunol Res 2015; 3:313-19Cross-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.Ding Y,…, Cao X. Nature Immunol 2016 Oct;17:1167–75.Image: https://commons.wikimedia.org/wiki/File:Non-small_cell_lung_carcinoma_--_high_mag.jpgThe 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.Reck M,…, Brahmer JR, M.D., for the KEYNOTE-024 Investigators. NEJM 2016 Oct 9; doi:10.1056/NEJMoa1606774.Image: Photo by David Dixon http://www.geograph.org.uk/photo/3492475Melanomas 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.Gao J, …, Sharma P. Cell 2016 Oct 6;167:397–404.Image: https://ghr.nlm.nih.gov/art/large/squamous-cell-carcinoma.jpegPatients 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.Ferris RL,…, Gillison ML. NEJM 2016 Oct 9; doi: 10.1056/NEJMoa1602252.Image: Türeci, Ö,…, Sahin U. Clin Can Res 2016; 22: 1885–96The 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.Liepe J,…, Mishto M. Science 2016 Oct 21;354:354–8.Image: https://commons.wikimedia.org/wiki/File:Myeloblast_with_Auer_rod_smear_2010-01-27.JPGNK 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.Romee R,…, Fehniger TA. Science Transla Med 2016 Sept 21; 8:357ra123.