PD-L1 is a defense mechanism by the tumor. PD-

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PD-L1 is a defense mechanism by the tumor.

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PD-L1 is expressed on a wide variety of the body's cells. Its original purpose is to keep an out of control immune system from destroying normal cells, like when sepsis occurs. Tumor cells just hijack PD-L1 to keep themselves from being destroyed.

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But if leronlimab brings in T cells and PD-L1 rises, it could make the tumor sensitive to PD-1 inhibitors? This how I understand it?

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The whole problem with cold tumors is a very low level of killer T-cells, the immune system not recognizing tumor cell antigens or the immune system not developing antibodies to any tumor antigens. This can be induced by Tregs, IL-10 and other M2 macrophage inducing factors not related to PD-L1.

Expression of PD-L1 further ramps up neutralization of immune response by blocking recognition of antigens and switching the immune system to an M2 (anti-inflammatory, anti- killer T-cell response).

Leronlimab switches the immune system from an M2 to M1 phenotype that increases killer T-cells and enhances antigen recognition and antibody development. Regardless of the presence of PD-L1.

PD-L1 inhibitors are only necessary when you have elevated levels of PD-L1. In cold tumors PD-L1 inhibitors add no benefit because there's little PD-L1, the lack of immune response is from other factors which leronlimab addresses.

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( 88%) of patients who received a weekly dose of 525 mg or higher experienced a significant increase in PD-L1 expression on their CTCs over a 30-to-90-day period after starting leronlimab.

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I do have to wonder whether PD-L1 comes back down after 90 days even without PD-L1 inhibitors. It would indicate that leronlimab is turning the tumor hot (high immune activity) which initially increases PD-L1 and then lowers PD-L1 after that. If so checkpoint inhibitors might be warranted for only a small amount of time.