Article Recommendations from Our Deputy and Senior Editors

Reduced bioenergetics in tumors and chronic infection lead to metabolic dysfunction and CD8⁺ T-cell exhaustion

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.

Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity

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.

CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity

Image : Jacoby et al., Nat. Comms. Fig. 2f

When 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.

CXCR5⁺ CD8⁺ T cells in chronic infection proliferate upon PD-1 blockade

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.

Oxygen sensing by T cells establishes an immunologically tolerant metastatic niche

Image : https://en.wikipedia.org/wiki/Oxygen_sensor#/media/File:Diving_oxygen_analyser.JPG

Tumor 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.

Tumor-specific T cell dysfunction is a dynamic antigen-driven differentiation program initiated early during tumorigenesis

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.