And check out exciting new work from the Oliver lab
@tgoliver.bsky.social showing that KLF4 promotes a KRT13+hillock-like state in squamous lung cancer👇:
www.biorxiv.org/content/10.1...

Finally, we are grateful for our funding sources:
DoD, ALA, CPRIT, NCI, Welch Foundation, and V Foundation.

This work was led by my student Hari Shankar Sunil (who defended his thesis last week and is now officially Dr. Sunil). Special THANKS to all our AMAZING collaborators: Trudy Oliver @tgoliver.bsky.social, Jinming Gao, Tae Hyun Hwang, Ralph DeBerardinis @rjdlab.bsky.social, John Minna, et al.

Collectively, our results demonstrate that TMPRSS11B promotes an acidified and immunosuppressive microenvironment. This work also nominates this enzyme as a promising therapeutic target in squamous lung cancer.

Utilizing ultra-pH-sensitive nanoparticle imaging and in vivo metabolite analysis, we identify regions of acidification, elevated lactate, and enrichment of immunosuppressive macrophages in LUSC tumors.

RNA FISH and spatial transcriptomics in the Rosa26-Sox2-Ires-GfpLSL/LSL; Nkx2-1fl/fl; Lkb1fl/fl (SNL) model reveal an enrichment of Tmprss11b expression in lung squamous tumors (LUSCs), specifically in Krt13+ hillock-like cells.

In our new study, we show that TMPRSS11B depletion reduces tumor burden and triggers an infiltration of immune cells in immunocompetent mice.

We initially identified TMPRSS11B in a Sleeping Beauty transposon mutagenesis screen (PMID:30463017). Our prior work showed that TMPRSS11B promotes the transformation of human bronchial epithelial cells and enhances lactate export from human lung squamous cell carcinoma cells.

Congratulations Trudy and Abbie, et al! Beautiful work!

Congratulations Niladri!!

Congratulations!!!

Congratulations Debbie! Exciting news!

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

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.