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Abstract

Image : https://commons.wikimedia.org/wiki/File%3AMitochondria.svg. Nevit (own work)In tumor microenvironments and during chronic inflammation, cytotoxic T cells become “exhausted.” Bengsch et al. and Scharping et al. found that the exhaustion involved repression of mitochondrial replication and energy production, orchestrated by reductions in PGC1α expression.Bengsch B,…, Wherry, EJ. Immunity 2016 Aug 16;45:358–73.Scharping NE,….Delgoffe GM. Immunity 2016 Aug 16; 45:374–88.Image : https://commons.wikimedia.org/wiki/File:Medulloblastoma_HE_x200.jpg. Jensflorian (own work)Cdk5 is expressed in medulloblastomas. Deleting Cdk5 allowed a potent CD4+ T cell–mediated tumor rejection to develop. The tumor immunoevasive mechanism evoked by interferon-γ that increases PD-L1 expression was suppressed in medulloblastomas that did not express Cdk5.Dorand RD,…, Petrosiute A. Science 2016 July 22; 353:399–403.Image : Jacoby et al., Nat. Comms. Fig. 2fWhen CD19 CAR T-cell therapy is used against ALL, the CD19 protein is often downregulated. This was found not to be the mere disappearance of an epitope, but represented cellular reprogramming and a switch to the myeloid lineage.Jacoby E,…, Fry TJ. Nat Comms 2016 Jul 27. doi: 10.1038/ncomms12320.Image : https://commons.wikimedia.org/w/index.php?curid=4463752. Gleiberg (own work)Less than 2% of CD8+ T cells express CXCR5. These cells were found to be generated in chronically infected animals and to have stem cell-like renewal properties. They could also differentiate into CXCR5− cells and proliferate extensively upon PD-1 blockade with checkpoint inhibitors.Leong YA,…, Yu D. Nat Immunol 2016 Aug 3. doi:10.1038/ni.3543.Im SJ,…, Ahmed R. Nature 2016 Aug 2. doi: 10.1038/nature19330.He R,…, Ye L. Nature 2016 Aug 2. doi: 10.1038/nature19317.Image : https://en.wikipedia.org/wiki/Oxygen_sensor#/media/File:Diving_oxygen_analyser.JPGTumor metastasis requires the maintenance of favorable protumor niches. T cells use the oxygen-sensitive PHD proteins to regulate differentiation and effector function. In lung tumors, PHD proteins promoted T-cell localization and Treg proliferation and repressed antitumor activity.Clever D,…, Restifo NP. Cell 2016 Aug 25;166:1117–31.e14.Image : https://commons.wikimedia.org/w/index.php?curid=9051744. Nephron (own work)T cells specific for tumors are often functionally disabled, and this has been attributed to the tumor microenvironment. Schietinger et al. found that this dysfunctional state is induced early in tumorigenesis, is intrinsic, and becomes irreversible over time.Schietinger A,…, Greenberg PD. Immunity 2016;45:389–401.