Máté Manczinger

Five mutational “fingerprints” could help predict how visible tumours are to the immune system Researchers from the HUN-REN Szeged Biological Research Centre and HCEMM have just published a new study suggesting that it’s not simply the number of tumour mutations that matters for immunothe...

A brief summary of our recent paper:
"Five mutational “fingerprints” could help predict how visible tumours are to the immune system"
eurekalert.org/news-release...

Link to our paper:
link.springer.com/article/10.1...

#Cancer #CancerResearch #Science

9/ Takeaway: Protein-level mutation patterns provide a complementary lens to DNA mutational signatures—linking mutagenesis + repair defects to peptide properties, immune contexture, and therapy response.

8/ But there’s nuance inside AAS4:
Among AAS4-driven tumors, specific HLA variants are enriched in immune-hot cases.
So antigen presentation genetics may modulate whether an AAS4 tumor ends up “cold” vs “hot.”

7/ One signature stood out clinically: AAS4.
AAS4 is associated with predominantly immune-cold tumors, poor prognosis, and limited response to immune checkpoint blockade.

6/ That biophysical bias matters for immunology.
By shaping the properties of mutated peptides, AASs can influence neopeptide immunogenicity → and, downstream, the tumor immune microenvironment.

5/ Next: not all amino acid substitutions are equal.

Different AASs preferentially generate amino acids with distinct biophysical properties (think charge, polarity, size).

4/ Why does that matter?
Because it suggests the protein-level consequence can converge even when the DNA-level cause differs.

3/ Importantly, these AASs aren’t a 1:1 readout of any single DNA mutational process.

The same AAS can be produced by multiple, largely unrelated exogenous + endogenous mutagenic processes.

2/ ~82% of tumor samples are dominated by a single AAS.

So despite massive heterogeneity, most cancers have one main “protein-mutation style.”

1/ Cancer mutations look chaotic—different tumors, different genes, different DNA changes.

But at the protein level, we found surprising order.
Introducing amino acid substitution signatures (AASs): 5 recurrent patterns that repeatedly show up across cancers.

Five dominant amino acid substitution signatures shape tumour immunity - Molecular Systems Biology Although numerous mutational processes operate in cancer, their functional impacts are unclear. We hypothesised that certain mutation sources preferentially generate amino acid substitutions that evad...

Our new paper is out:

Five dominant amino acid substitution signatures shape tumour immunity

link.springer.com/article/10.1...

Thread 🧵⬇

#cancer #tumor #immunity #immunotherapy #oncology

C > U mutations generate immunogenic peptides in SARS-CoV-2

APOBEC enzymes—key players of the innate immune system—induce mutations that become fixed in viral genomes and enhance immune recognition.

nature.com/articles/s41...

#COVID_19 #Immunology #virus #infectiousdiseases #vaccine #Genetics

C > U mutations generate immunogenic peptides in SARS-CoV-2 @natcomms.nature.com @matemanc.bsky.social
@csabapallab.bsky.social
www.nature.com/articles/s41...

I C U mutant!

Our new paper is out! Our immune system doesn’t just fight viruses – it edits them.
APOBEC enzymes introduce C>U mutations that often make viral proteins easier for HLA molecules and T-cells to detect, boosting immune recognition.
nature.com/articles/s41...
#COVID_19

I C U mutant!

Our new paper is out! Our immune system doesn’t just fight viruses – it edits them.
APOBEC enzymes introduce C>U mutations that often make viral proteins easier for HLA molecules and T-cells to detect, boosting immune recognition.
nature.com/articles/s41...
#COVID_19

www.pnas.org/doi/10.1073/...

How cancer arises: Genetics releases, plasticity creates, genetics stabilizes