Thrilled to finally see my PhD work from the Bosenberg Lab published in this month's issue of #CancerImmunologyResearch !! 1/n aacrjournals.org/cancerimmuno... - ThreadSky

mk-mcg5.bsky.social • 27 days ago

Thrilled to finally see my PhD work from the Bosenberg Lab published in this month's issue of #CancerImmunologyResearch !! 1/n
https://aacrjournals.org/cancerimmunolres/article/13/2/245/751248/Setdb1-Loss-Induces-Type-I-Interferons-and-Immune

Comments

virusesimmunity.bsky.social•24 days ago

Congratulations Meaghan!

mk-mcg5.bsky.social•27 days ago

Here we describe the in vivo CRISPR screen using our immunogenic melanoma cell line model, YUMMER-G. Our screen adds to the literature on Setdb1 as a tumor-intrinsic mediator of anti-tumor immunity (among other hits!) 2/n

mk-mcg5.bsky.social•27 days ago

Setdb1 is the H3K9 methyltransferase associated with the HUSH complex, which suppresses expression of transposable elements such as ERVs. In validating our screen, we found that tumors lacking Setdb1 are completely and efficiently cleared in a CD8+ T cell dependent manner. 3/n

mk-mcg5.bsky.social•27 days ago

We found that the mechanism of this is likely twofold: Setdb1 loss makes melanoma cells more immunogenic via a type-I interferon loop induced by re-expressed ERVs. This results in increased T-cell infiltration and activation leading to tumor clearance. 4/n

mk-mcg5.bsky.social•27 days ago

Secondly, we hypothesized that these ERVs might also serve as antigens. We detected ERV-reactive T cells in Setdb1-/- tumors, and further showed that some animals who have cleared Setdb1-/- tumors can subsequently clear MC38 tumors that express the same ERV antigen. 5/n

mk-mcg5.bsky.social•27 days ago

I'm hopeful that this work will inform future studies and ideas for improving immunotherapy responses, including by targeting regulators of ERV expression and learning more about these pathways in human cancer! 6/n

mk-mcg5.bsky.social•27 days ago

So grateful to numerous collaborators and co-authors who made this work happen and got our paper to the finish line! 🧬🐭 @ericsongg.bsky.social @tcellogic.bsky.social @calderwoodlab.bsky.social @virusesimmunity.bsky.social

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