Of course you know I still think this "Can ICI cause

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twinter11 sherlock57 #160012
591
Of course you know I still think this

"Can ICI cause ccr5 to upregulate"
(I would bet money on it)

I think Leron is going to be considered regardless of pdl1 +-
Or whether ccr5 +-
Or even in cases where only chemo or pre surgery (for various reasons) or whatever.
But Im no oncologist


"Yes,
immune checkpoint inhibitor (ICI) treatment can cause an upregulation of CCR5 and its associated ligands (such as CCL5).

This upregulation is linked to the increased activation of immune cells (particularly CD8+ T cells) that occurs when checkpoints like PD-1 or CTLA-4 are blocked.

Here is a breakdown of the evidence regarding ICIs and CCR5:

Mechanism of Upregulation:
ICI therapy (anti-PD-1/CTLA-4) boosts the immune system, resulting in the upregulation of specific chemokine receptors, including CCR5 and CXCR3, along with their ligands (CCL5, CXCL9/10), which are necessary for T-cell trafficking to tissues.

Role in Toxicity (IRAEs):
In cases of ICI-induced myocarditis, there is a significant increase in specialized effector CD8+ T cells (Temra cells) in the blood and heart, which express higher levels of CCR5.

Immune Resistance:
While this upregulation is part of the immune response, it can also lead to the infiltration of regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs) that express CCR5, contributing to a "cold" tumor environment and potential resistance to ICIs.

Therapeutic Combination:
Because ICIs can induce this inflammatory response, researchers are investigating combining ICI therapy with CCR5 blockers (like leronlimab or maraviroc) to prevent this unwanted upregulation, reduce side effects (like cardiotoxicity), and enhance the anti-tumor effect".

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