Kate O'Donnell

Congratulations Debbie! Exciting news!

It was a pleasure to speak to our SURF students - thank you for the invite Dr. Diaz!

Thank you @aacrjournals.bsky.social for selecting our story for the cover of Cancer Research!

A special thanks to ALL our collaborators for their important contributions to this work and to NIH/NCI, CPRIT, V Foundation, Welch Foundation, and DoD for their support, and I’m excited that our submission was selected for the cover (credit: Jose Cabrera)!

Collectively, our studies uncover a novel mechanism by which two immune checkpoint proteins are coordinately regulated and suggest a new therapeutic strategy for lung cancer patients.

Finally, we showed that ISR activation accelerates tumorigenesis and inhibits T cell function, effects that can be overcome by combining PD-1 and TIGIT blockade with the ISR inhibitor ISRIB.

Our analysis of primary human lung tumors identified a significant correlation between PD-L1 and CD155 expression. This is particularly interesting because other groups have shown that CD155 expression is associated with resistance to anti-PD-1 therapy in lung cancer.

Here we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. We show that CD155 and PD-L1 are coordinately induced by the ISR, enhancing translation of both immune checkpoints through bypass of inhibitory uORFs in their 5' UTRs.

The ISR is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. We previously showed that ISR activation potently induces Programmed Death Ligand 1 (PD-L1), leading to suppression of anti-tumor immunity (Suresh et al, Nature Cancer, 2020).

The Integrated Stress Response (ISR) Pathway Coordinates Translational Control of Multiple Immune Checkpoints in Lung Cancer url: aacrjournals.org/cancerres/ar...

This is my first post here. The past few months have been challenging for science, but I enjoy learning about others' work here and wanted to share our latest study. Congrats to postdoc Shayna Thomas-Jardin on her outstanding work published in Cancer Research @theaacr.bsky.social