Ive been thinking about this for a bit. And AI'd
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Posted On: 10/26/2025 5:14:29 PM
Ive been thinking about this for a bit.
And AI'd it before. But thought I would post.
it makes me wonder that after additional research, its determined that it might be beneficial to treat with Leronlimab after ICI even in non CCR5+ tumors
do pdl1 blockers cause inducement of ccr5?
AI summary:
"Recent research indicates that while
PD-L1 blockers do not directly induce CCR5, blocking the PD-1/PD-L1 pathway can create an immunosuppressive feedback loop that increases the expression of CCR5 on certain T-cells. This upregulation of CCR5 can promote an immunosuppressive environment that limits the effectiveness of PD-L1 inhibitors.
The mechanism linking PD-L1 blockade and CCR5
The connection between the two pathways occurs as a negative feedback loop within the tumor microenvironment:
1. PD-L1 blockade activates anti-tumor immunity: When PD-L1 inhibitors are administered, they block the inhibitory PD-1/PD-L1 signal, "releasing the brakes" on anti-tumor T-cells. This allows the immune system to attack cancer cells.
2. Increased T-cell activity triggers an immunosuppressive response: The heightened immune activity in the tumor microenvironment can cause the release of pro-inflammatory cytokines, which in turn can lead to the activation of neutrophils.
3. Neutrophils recruit immunosuppressive CCR5+ T-cells: The activated neutrophils then secrete CCR5 ligands, which recruit immunosuppressive CCR5+ T-cells to the tumor.
4. CCR5+ T-cells reduce anti-tumor effect: The accumulation of these CCR5+ T-cells counteracts the positive effects of the PD-L1 blockade, contributing to immune evasion and therapy resistance.
The interplay of CCR5 and PD-L1 in cancer
Numerous studies show that blocking CCR5 in combination with PD-L1 inhibitors can improve anti-tumor responses and overcome resistance.
- Enhancing immunotherapy: Combining CCR5 inhibition with PD-L1 inhibitors has shown enhanced efficacy in preclinical studies involving gastric and colon cancers.
- Overcoming resistance: High expression of CCR5 is associated with resistance to PD-1/PD-L1 checkpoint inhibitors in triple-negative breast cancer (TNBC). Targeting CCR5 can help overcome this resistance and improve long-term survival.
- Modulating the tumor microenvironment: The CCR5-CCL5 axis can allow cancer cells to evade the immune system by altering immune cell function and enhancing PD-L1 expression. Inhibiting CCR5 helps reverse this process
And AI'd it before. But thought I would post.
it makes me wonder that after additional research, its determined that it might be beneficial to treat with Leronlimab after ICI even in non CCR5+ tumors
do pdl1 blockers cause inducement of ccr5?
AI summary:
"Recent research indicates that while
PD-L1 blockers do not directly induce CCR5, blocking the PD-1/PD-L1 pathway can create an immunosuppressive feedback loop that increases the expression of CCR5 on certain T-cells. This upregulation of CCR5 can promote an immunosuppressive environment that limits the effectiveness of PD-L1 inhibitors.
The mechanism linking PD-L1 blockade and CCR5
The connection between the two pathways occurs as a negative feedback loop within the tumor microenvironment:
1. PD-L1 blockade activates anti-tumor immunity: When PD-L1 inhibitors are administered, they block the inhibitory PD-1/PD-L1 signal, "releasing the brakes" on anti-tumor T-cells. This allows the immune system to attack cancer cells.
2. Increased T-cell activity triggers an immunosuppressive response: The heightened immune activity in the tumor microenvironment can cause the release of pro-inflammatory cytokines, which in turn can lead to the activation of neutrophils.
3. Neutrophils recruit immunosuppressive CCR5+ T-cells: The activated neutrophils then secrete CCR5 ligands, which recruit immunosuppressive CCR5+ T-cells to the tumor.
4. CCR5+ T-cells reduce anti-tumor effect: The accumulation of these CCR5+ T-cells counteracts the positive effects of the PD-L1 blockade, contributing to immune evasion and therapy resistance.
The interplay of CCR5 and PD-L1 in cancer
Numerous studies show that blocking CCR5 in combination with PD-L1 inhibitors can improve anti-tumor responses and overcome resistance.
- Enhancing immunotherapy: Combining CCR5 inhibition with PD-L1 inhibitors has shown enhanced efficacy in preclinical studies involving gastric and colon cancers.
- Overcoming resistance: High expression of CCR5 is associated with resistance to PD-1/PD-L1 checkpoint inhibitors in triple-negative breast cancer (TNBC). Targeting CCR5 can help overcome this resistance and improve long-term survival.
- Modulating the tumor microenvironment: The CCR5-CCL5 axis can allow cancer cells to evade the immune system by altering immune cell function and enhancing PD-L1 expression. Inhibiting CCR5 helps reverse this process
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