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PD-L1 (programmed death ligand one) is typically u

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Post# of 154850
(Total Views: 469)
Posted On: 07/02/2025 12:31:46 AM
Posted By: ohm20
Re: chazzledazzle #154764
Quote:
PD-L1 (programmed death ligand one) is typically used to signal the human bodies immune system to see a tumor and bring death to the cancer.

What many solid tumors do in the biochemistry of the tumor microenvironment is lessen, or down regulate, the amount of PD-L1 in that environment...

ith PD-L1 being so low in serum, tumors are masked, and considered cold. Because nothing is happening there except they have successfully defeated the bodies Pd-L1 signaling abd the tumor can grow and metastasize at will.



It's the opposite of that. When PD-L1 binds to PD-1 it dampens antigen response from M1 (tumor killing) macrophages so they don't kill off the tumor cells. It also switches over macrophage response from M1 macrophages to M2 (tumor protectant) macrophages in cancer more commonly known as Tregs (T- regulatory cells).

Cold tumors are considered cold because of the lack of M1 macrophages in the tumor microenvironment. Which allows the tumor to thrive and not be killed off by the M1 macrophages, Hot tumors are hot because of increased M1 macrophage activity although tumor protectants can still stave off tumor destruction. The tumor cells themselves can induce tumor protectants to flourish.

Leronlimab flips things around. It changes things from an M2 (protectant) macrophage phenotype to M1 (killer) macrophage by downregulating IL-13, IL-10 and IL-4. But in response as shown in the 60 day window in the mTNBC results there is a corresponding increase in PD-L1. That response is an attempt to control the initial overwhelming amount of M1 macrophages. Bring in a PD-L1 or PD-1 downregulator and what you have is unprotected tumor cells being killed off by the M1 macrophages. After that 60 day window what is most likely happening is a return to a more homeostatic state.


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