Comment by antichronology

15 hours ago

This is really interesting - I'm going to be honest I'm not an immunologist so this is my (LLM assisted) understanding of your comment:

The immune system recognizes a sugar as a PAMP, or Pathogen-Associated Molecular Pattern, which is a signature of a potential microbial threat.

This initiates pyroptosis an inflammatory form of programmed cell death causing the cell to burst. This rupture releases tumor antigens and DAMPs (Damage-Associated Molecular Patterns), which are "danger signals" from the dying cell

The release of DAMPs shifts the Tumor Microenvironment (TME) from an immunologically "cold" to a "hot" state, promoting a potent Type I Interferon (IFN-I) response.

This response recruits Antigen Presenting Cells (APCs), which engulf the newly released tumor antigens.

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mRNA vaccines are somewhat of a parallel approach where the antigen selection and delivery happens manually. An mRNA vaccine delivers the encoding sequence for specific tumor antigens to drive production and presentation, training the immune system. One of the big challenges of this space is optimal antigen selection from the patient's tumor.

One thing I'm not fully clear on is why only tumor cell react to PAMP instead of healthy cells. Could be a promising approach but molecular biology is pretty tricky and the devil is always in the details.

1 comment

antichronology

JPLeRouzic 4 hours ago

> "why only tumor cell react to PAMP instead of healthy cells"

I am not a scientist, but I believe that "normal" cells do not seek long-chain alien sugars like those produced by ocean bacteria. Conversely, "cancerous" cells may find these uncommon sugars appealing, and they consume sugar eagerly (Warburg effect).

After the alien sugars are metabolized, fragments migrate to the cell membrane and might be recognized by the immune system as foreign.

The fact that large molecules trigger Pyroptosis may be helpful.