There have been some discussions about the importance (or not) of our cold-hot tumor claim for which the PD-1/PDL-1 axis is a key factor both, as an indication, and as a potential market in this highly competed/researched market.
The following remarks are not new material and are sourced from the following link (I believe it has been shared here before):
Cold and hot tumors: from molecular mechanisms to targeted therapy | Signal Transduction and Targeted Therapy
https://www.nature.com/articles/s41392-024-01979-x
I am awaiting the PDL-1 related numbers with great expectation. The potential market is huge, but, more importantly, i.m.h.o, it will provide [color=rgb(55, 90, 230)]VALIDATION[/color] to Leronlimab.
We all know CCR5 signaling help cancer cells to migrate, invade and metastasize by recruiting Tregs and tumor-associated macropages (TAMS) instead of cytotoxic T cells. These cells cluster in the tumor periphery, forming a barrier that prevents the T (CD8) cells from entering. The hallmark of immune-excluded CRC.
Additionally, CCR5 mechanisms suppress dendritic cell function (via chemokines TGF-B, L-10) and increases PD-L1 expression . Also, the CCR5-dependent chemokine gradient gets distorted resulting in T-cells entrapment at the tumor edge.
In the context of CRC : This is one of the cancers most prone to immune exclusion. Its phenotype is shifted towards COLD making it resistant to PD-1/PD-L1 therapy.
In summary, if Leronlimab works, it will block CCR5 resulting in less TME (tumor Microenvironment) suppression producing a more effective anti-tumor immunity allowing/enhancing PD-1/PD-L1 therapy. The reduced tumor burden will yield a falling ctDNA.
But I digress. The PD-L1 is an important marker indicating immune suppression by its dominance (or lack of) on tumor and/or myeloid cells.
Is part of the mechanism-of-action, is part of telling us: Leronlimab works !! So, I disagree with those that think these readings are irrelevant or not important.
They are.
The following remarks are not new material and are sourced from the following link (I believe it has been shared here before):
Cold and hot tumors: from molecular mechanisms to targeted therapy | Signal Transduction and Targeted Therapy
https://www.nature.com/articles/s41392-024-01979-x
I am awaiting the PDL-1 related numbers with great expectation. The potential market is huge, but, more importantly, i.m.h.o, it will provide [color=rgb(55, 90, 230)]VALIDATION[/color] to Leronlimab.
We all know CCR5 signaling help cancer cells to migrate, invade and metastasize by recruiting Tregs and tumor-associated macropages (TAMS) instead of cytotoxic T cells. These cells cluster in the tumor periphery, forming a barrier that prevents the T (CD8) cells from entering. The hallmark of immune-excluded CRC.
Additionally, CCR5 mechanisms suppress dendritic cell function (via chemokines TGF-B, L-10) and increases PD-L1 expression . Also, the CCR5-dependent chemokine gradient gets distorted resulting in T-cells entrapment at the tumor edge.
In the context of CRC : This is one of the cancers most prone to immune exclusion. Its phenotype is shifted towards COLD making it resistant to PD-1/PD-L1 therapy.
In summary, if Leronlimab works, it will block CCR5 resulting in less TME (tumor Microenvironment) suppression producing a more effective anti-tumor immunity allowing/enhancing PD-1/PD-L1 therapy. The reduced tumor burden will yield a falling ctDNA.
But I digress. The PD-L1 is an important marker indicating immune suppression by its dominance (or lack of) on tumor and/or myeloid cells.
Is part of the mechanism-of-action, is part of telling us: Leronlimab works !! So, I disagree with those that think these readings are irrelevant or not important.
They are.
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