Weekly Digests

2019

May

Turning Tregs From Enemies to Allies

May 29, 2019

T regulatory cells (Tregs) are known for their ability to suppress effector T cell functions in the tumor microenvironment. In an effort to better understand and possibly disrupt Treg-mediated immunosuppression, Di Pilato and Kim et al. investigated the CARMA1-BCL10-MALT1 (CBM) signalosome complex within Tregs. Interestingly, disruption of the CBM complex in all or...

Why does PD-1 blockade need CXCR3 signaling? It’s not what you think

May 22, 2019

Motivated to extend the benefit of PD-1 blockade to more patients, Chow et al. explored the role that chemokines play in resistance to anti-PD-1 and found that the chemokine receptor CXCR3 and its ligand CXCL9 were crucial for the response to anti-PD-1 therapy in mouse tumor models. The results were recently published in...

CTLA-4 and PD-1 set the limits on T cell differentiation

May 15, 2019

Positive and negative costimulatory molecules on T cells are known to play a role in T cell activation, however, whether they play a role in T cell differentiation (along with TCR signal strength and cytokine signaling) is not as well defined. Following observations that genetic loss or blockade of CTLA-4 can affect CD4+...

Targeting tumor collagen hits the immunotherapeutic sweet spot

May 8, 2019

While immune checkpoint inhibitors and cytokine treatments have demonstrated efficacy against several types of cancer, they frequently cause severe side effects due to excessive and widespread off-tumor activation of the immune system. In a paper recently published in Science Translational Medicine, Ishihara and Ishihara et al. aimed to decrease off-tumor toxicities by taking...

Too much of a good thing: why KIT inhibitors stop working

May 1, 2019

Constitutive signaling from a single mutation in the KIT proto-oncogene can be sufficient to drive the formation of a gastrointestinal stromal tumor (GIST). These tumors constitutively express immunosuppressive IDO, which dampens dendritic cell-primed effector CD8+ T cell responses. Previous studies have suggested that using imatinib, a small molecule Kit inhibitor that dampens IDO...

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