Richard Jenner

In this episode of the Epigenetics Podcast, we talked with Srinjan Basu from Imperial College London to talk about his work on how chromatin architecture and epigenetic mechanisms orchestrate developmental gene expression programs. #podcast #epigenetics

Listen here: activemotif.com/podcasts-sri...

We are recuiting two new Associate Professors here in Oxford Biochemistry. Come join us! Reach out to me if you have any questions. Please repost! tinyurl.com/mr3m7bd3

Interested in applying your molecular biology skills to improve tumour #immunotherapy?

@cruk-cityoflondon.bsky.social #PhD studentship available in my lab @ucl.ac.uk in collaboration with @diunguyenvnuk.bsky.social @qmbci.bsky.social

For more information and to apply: colcc.ac.uk/phd-students...

This work reveals mechanisms that regulate CD4+ TCTX function in tumours and highlights the potential therapeutic utility of targeting post-transcriptional regulatory pathways in T cells for the treatment of cancer. 8/8

Constitutive expression of Zfp36l1 in T cells nullified anti-tumour responses while knocking out Zfp36l1 and its paralogue Zfp36 released the block to GzmB protein production and promoted tumour control. 7/8

We found that the RNA binding proteins ZFP36L1 and ZFP36 block GzmB protein production and that Zfp36l1 must be downregulated for the therapeutic effects of anti-CTLA-4 and anti-LAG-3 plus anti-PD-1 treatments. 6/8

We characterised this poised TCTX state, finding CD4+ T cells differentiate into poised TCTX in response to type I interferon in a manner dependent on Blimp-1 and antagonised by Bcl6. But what blocks GzmB protein production? 5/8

We instead found that cytotoxic CD4+ T cells (TCTX) are already present in untreated tumours, but in a poised state in which GzmB and other effector genes are transcribed but not translated. 4/8

The Quezada lab has previously shown that CD4+ T cells gain cytotoxicity in response to anti-CTLA4 therapy and can drive tumour regression. We used scRNA-seq to identify the gene expression changes that underly this activity but surprisingly found very few genes change… 3/8

In addition to their well characterized helper function, tumour-infiltrating CD4+ T cells can also acquire cytotoxic activity. These cells hold promise as a therapeutic target but how their activity is regulated remains poorly understood. 2/8

A post-transcriptional regulatory checkpoint controls the response of tumor-infiltrating cytotoxic CD4+ T cells to immunotherapy Acquisition of cytotoxic activity in CD4+ T cells (TCTX) can promote potent anti-tumor activity thus holding promise as a therapeutic approach. However, how this activity is regulated remains poorly u...

Pleased to share our preprint describing a central role for #post-transcriptional processes in the response to cancer #immunotherapy. Huge amount of work led by Maria Vila de Mucha and @juliahlond.bsky.social with Sergio Quezada and @martint-babraham.bsky.social 1/8

www.biorxiv.org/content/10.1...