Abnormal RNA processing in cancer offer an immunotherapy target

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See the diagram at the end of the page:

In normal cells (a), cellular machinery removes non-coding sequences called introns from immature mRNA and joins coding sequences called exons together in a process called splicing.

The resulting mRNA sequence is used to guide the formation of an amino-acid chain that makes up a protein.

In a tumour (b), splicing can go wrong.

In those instances, the cells produce incorrect or unusual proteins.

The proteins produce structures called neoantigens, which flag the cells to the immune system as ‘foreign’. (Nature News & Views | 7 min read, Nature paywall)

https://www.nature.com/articles/d41586-025-00302-0?utm_source=Live+Audience&utm_campaign=65192fafeb-nature-briefing-daily-20250220&utm_medium=email&utm_term=0_b27a691814-65192fafeb-498702756

Peptides from abnormal RNA processing in cancer offer an immunotherapy target

19 February 2025

Tumour cells often have problems processing messenger RNA. The finding that these splicing errors result in commonly expressed peptides that are recognized by immune cells offers a target for cancer treatments.

Cancer cells are recognized by the immune system as being distinct from normal tissues because they present immune-stimulatory peptides, known as neoantigens, that are derived from proteins encoded by mutated genes.

A common mechanism of resistance to immunotherapies is the low abundance and lack of widespread expression of these neoantigens in a tumour.

An ideal tumour neoantigen would be uniformly expressed across all tumour cells, efficiently processed and presented on the surface of the cell for recognition and activation by immune-system T cells, and be a target found in many people who have cancer.

Writing in "Nature", Kwok et al.1 present an extensive survey of RNA-sequencing results for tumour cells reported in databases.

The authors highlight the potential of a largely underexplored class of neoantigens derived from abnormal processing of messenger RNA in tumour cells across multiple cancer types.

This discovery reveals new avenues for targeting these neoantigens in cancer immunotherapies.

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