IFNy TEMPORARILY actives the pathway that activate

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IFNy TEMPORARILY actives the pathway that activates PD-L1. Clearly CYDY is hoping that PD-L1 expression is not temporary, because the option to use ICIs can only happen a number of months later. Does the temporary activation of PD-L1 mean that the EXPRESSION is also temporary -- meaning that ICIs would have to be utilized at that time and not later?

I believe I've heard that some of the scientists at CYDY think that once its expression is elevated, PD-L1 will not revert. Is that true?

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The lack of complete data from our trials or any other source I've ever ran across leaves me to rely on deduction based on what I do know. That initial switch to a very large amount of M1 macrophages leads to that increase in IFNY and in response you see the rise in PD-L1. Over a longer time you'll see a decrease in M1 macrophages due to immune system exhaustion but substantially more than you'd see in a cold tumor situation. You'd still see an increased PD-L1 expression compared to cold tumors but not as high as the initial surge. The use of ICIs would still be indicated in that situation.

Not having PD-L1/PD-1 inhibitors from the beginning is not a great situation because most of the tumor killing is almost certainly happening in the first 6 months to 1 year. After that time period it's just a mop up operation of any remaining tumor cells. Having the inhibitors in place from the start would increase that initial kill rate.

From the original results from just the mTNBC trial we know leronlimab works damn well even without the ICIs. Unfortunately with the late stage/late line treatment we have in our trial leronlimab probably will not be able to keep progression at bay for the full year of the trial for all patients. It should be able to for most of them until the leronlimab/ ICI combination kicks in on the follow up. I can understand why the FDA wants a "clean" trial with just leronlimab but I still want to launch a long list of expletives against them for not allowing ICIs from the start given the evidence we do have and that this a phase 2 trial that is by nature exploratory.