This seems so cool that I was immediately suspicious, but this isn't my area of expertise, so it's hard for me to understand the original paper:

https://www.nature.com/articles/s41551-025-01380-1

This is the abstract, though, which suggests the need for a standard "in mice" disclaimer:

> The success of cancer immunotherapies is predicated on the targeting of highly expressed neoepitopes, which preferentially favours malignancies with high mutational burden. Here we show that early responses by type-I interferons mediate the success of immune checkpoint inhibitors as well as epitope spreading in poorly immunogenic tumours and that these interferon responses can be enhanced via systemic administration of lipid particles loaded with RNA coding for tumour-unspecific antigens. In mice, the immune responses of tumours sensitive to checkpoint inhibitors were transferable to resistant tumours and resulted in heightened immunity with antigenic spreading that protected the animals from tumour rechallenge. Our findings show that the resistance of tumours to immunotherapy is dictated by the absence of a damage response, which can be restored by boosting early type-I interferon responses to enable epitope spreading and self-amplifying responses in treatment-refractory tumours.

Basically, seed tumors with IFN-1 using targeted RNA nanomolecules (that accumulated in the lungs in this case where they modeled lung cancers). This converts the tumor microenvironment from one hostile to immune cells to one where immune cells are now active and on the hunt for tumor specific neoantigens.

The one open question I wish they would get at is the exact sentization mechanism behind the PD-L1 inhibitor and IFN-1 response. The idea is that cancer cells have selective pressure to hide from the immune system and one way of doing that is presenting this PD-1 receptor to the PD-L1 ligand on the immune cell, an interaction that keeps the cancer cell from being killed and one that PD-L1 inhibitor drugs target to enable tumor cells to now be visible to the immune system (as they output a lot of screwed up things that are otherwise visible to the immune system as "not self").

They tested tumors that aren't sensitive to pd-l1 inhibition so presumably evading immune surveillance another way instead of presenting PD-1, and then found them to then be sensitive to PD-L1.

It could be that within a tumor there are subclonal cells that do express PD-1 but are otherwise protected from PD-L1 inhibitiion having any effect from the hostile tumor microenvironment keeping immune surveillance from operating normally anyhow. Induce the immune response, now the T cell is in the area for PD-L1 inhibition to work. Another possibility is that the IFN-1 induction leads to PD-1 now being expressed by cells that didn't do it previously.

Authors didn't explore this though. Probably would take more experiments and mice are expensive and time consuming. It could be answered by single cell RNA sequencing of these unresponsive tumors and seeing if there is some subset of cryptic tumor cells that do express PD-1 already before IFN-1 induction. As well as measuring expression after IFN-1 induction (maybe several timepoints to measure change in gene expression profile in the tumor population, if any)

Something that "essentially tells the body to ... stimulate the immune system" usually would cause high fever? I didn't see this mentioned so wondering if it is or isn't a complication with this.

... in mice.

Don't get me wrong, it's encouraging to see research in this field progressing. But there is a long list of treatments that work in mice that do not work in humans.

I'll temper my enthusiasm with a healthy dose of pragmatism.

mRNA research. Something which the current government just cut funding across the board.

Isn't this literally the plot of I Am Legend? And we also have scientists thawing out 2.5 million year old ice, just to see what happens. smh

I still hate those articles title with all my heart.

Is there a way to ban lies about cancer vaccines, fusion reactors, and infinite battery storage ?

Sure, okay, people are working on that, and they're making small incremental improvements and that's good for them ; and unfortunately they need to advertise to secure more funding for the later incremental stage of their research. I understand that.

But please stop with the nonsensical "cancer vaccine", "miracle cancer treatment", "cancer breakthrough" etc... This is an insult to everyone who lost a loved one to cancer.

Cause I'll be _really_ happy when a _real_ cure happens (as in, when anyone can go the their doctor, for real, and get a real "cure", and they have no cancer after that, and it's a simple as getting a cure for, well, you know, the diseases that we "cure", and that are definitely not cancer ?)

But this is not today. Today we "deal" with cancer, we "spare" people some time, we squash it a bit and maybe save a couple of years if you have the "lucky" kind of cancer - and that's great, and let's continue doing that.

But enough with the headlines.

Play it like Apple, please.

Tell me about it when I can buy it.

I miss the old @justsaysinmice twitter (account deleted)

https://www.statnews.com/2019/04/15/in-mice-twitter-account-...

I know a lot of people here are tired of these teaser headlines and don't want to be told anything until there's an actual cure. But here me out - I'm old enough to have lost several friends and family to cancer. Along the way there have always been headlines like this where it seems that a breakthrough is imminent, and you know what? We are much better at preventing, detecting, and treating cancer than we were 40 years ago!

I personally know several people who have gotten breast cancer and survived! I remember when that was practically a death sentence. Ditto for colon cancer. Even your prospects for lung cancer have improved dramatically.

What has made this progress possible is this relentless research. Research that leads to reports being published. Promising leads being discussed. A huge portion of this research leads to dead ends - BUT - some leads to real progress and has in turn lead to real lives being saved. So I say continue with the research and continue publishing and sharing the research results.

The leap from mice to human might be greater than from nothing to mice.

The clickbait title serves as a boost to researcher's motivation.

yet another paywalled research making headline, at least allow me to read it or share pdfs.