Quote:Not even getting into radiation here, but DNA repair absolutely matters in this conversation.
Either way, chemo is doing something important — it keeps pressure on the tumor and keeps things from getting out of control while you’re trying to set up anything immune-related.
You pull that out and go LRM → ICI, what exactly is controlling the disease in that window? The tumor just sits there and cooperates? That’s not how this works.
And if you’re not thinking about what’s happening in the microenvironment while this is going on — trafficking, suppression, antigen presentation — you’re going to come to the wrong conclusion pretty fast. We’ve already seen that in a few posts.
What keeps pressure on the tumors is an immune system with activated CD8 and CD4 T-cells ready to kill off tumor cells. In cold tumors those cells are far less numerous and those that do exist are blocked by immune checkpoints like PD-L1. Leronlimab increases those CD8 and CD4 T-cells with leronlimab downregulating at least 4 immune checkpoints. I suspect it also downregulates some other immune checkpoints that haven't been tested for. Those immune checkpoints are what help keep antigen presentation at bay. Tumor killing is not wholly dependent on antigen presentation because natural killer immune cells will do so without antigen presentation and leronlomab also increases NK cells. PD-L1 is a substantial immune checkpoint which is why we need the addition of a PD-1 or PD-L1 inhibitor to really strip down tumor defenses.
Leronlimab also breaks DNA repair which is helpful even in the absence of radiation or chemotherapy because sometimes immune cells will only damage but not kill tumor cells. Then of course there's reducing the motility of CTCs and reducing CAMLs and decreasing VEGF to stop tumor blood vessel growth.
Chemotherapies generally have a single weapon at their disposal damaging DNA sometimes leading to cell death or reduction in cell division. Nice, but sometimes fail over time especially if metastasis is present. Leronlimab has an arsenal at its disposal all controlled by modifying the faults in the body's own immune system that allow a tumor to proliferate. Chemotherapy may give a boost to leronlimab in killing the tumor faster, but the body's own immune cells are very proficient in their own when they're not being hindered.
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