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

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...