Tech.Cm, you asked about feeding the Munich poster

Tech.Cm, you asked about feeding the Munich poster info about PD-L1 to Gemini (Google's AI) like I did to ChatGPT.

I asked the following question to Gemini (2.5 Flash):

"How does Leronlimab turn cold tumors hot for checkpoint inhibitors to work?"

I will post the entire answer below. Gemini already knows about PD-L1.

Quote:

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"Cold" tumors are characterized by a lack of immune cell infiltration, making them less responsive to immunotherapy, particularly checkpoint inhibitors. "Hot" tumors, on the other hand, have a robust immune presence, which allows checkpoint inhibitors to effectively unleash the body's immune system to attack cancer cells.

Leronlimab is an investigational humanized monoclonal antibody that targets C-C chemokine receptor type 5 (CCR5). While its full mechanism of action in "turning cold tumors hot" is still being investigated, here's what current research suggests:

CCR5's Role in the Tumor Microenvironment: CCR5 is a receptor expressed on various immune cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), as well as on some cancer cells themselves. These cells are known to create an immunosuppressive tumor microenvironment, contributing to the "cold" phenotype.

Immune Cell Trafficking: CCR5 plays a critical role in guiding immune cells to sites of inflammation and, unfortunately, also to tumors. By blocking CCR5, leronlimab may alter the trafficking of these immunosuppressive cells into the tumor, thereby reducing their inhibitory effects.

M2 Macrophage Reprogramming: Some research suggests that CCR5 inhibition can reprogram M2 macrophages (tumor-promoting macrophages) into M1 macrophages (anti-tumor macrophages), which actively fight cancer.

Treg Modulation: By blocking CCR5, leronlimab may also disrupt the function of Tregs, which are immune cells that suppress anti-tumor immune responses, effectively "turning off" the immune system's ability to fight cancer.

Increased PD-L1 Expression: Recent data from CytoDyn, the developer of leronlimab, indicates that leronlimab treatment correlates with an increased expression of programmed death-ligand 1 (PD-L1) on circulating tumor cells (CTCs) in patients with metastatic Triple-Negative Breast Cancer (mTNBC).

PD-L1 and Checkpoint Inhibitors: PD-L1 is a protein found on cancer cells and immune cells that helps tumors evade the immune system by binding to PD-1 on T cells, essentially putting the brakes on the immune response. Checkpoint inhibitors work by blocking this interaction, allowing T cells to attack the cancer.

"Hot" Tumor Induction: The observed increase in PD-L1 expression after leronlimab treatment suggests that leronlimab may be inducing an "inflamed" or "hot" tumor environment. This elevated PD-L1 level could then make these tumors more susceptible to the effects of immune checkpoint inhibitors.

Synergistic Potential with Checkpoint Inhibitors: The idea is that by making "cold" tumors "hot" through mechanisms like increased PD-L1 expression and modulating the immune suppressive cells, leronlimab can prime the tumor microenvironment to be more receptive to checkpoint inhibitors, leading to a more effective anti-tumor immune response. This combination approach aims to overcome the resistance often seen in "cold" tumors to checkpoint inhibitor monotherapy.

In summary, leronlimab's potential to turn "cold" tumors "hot" for checkpoint inhibitors to work appears to involve:

Modulating the tumor microenvironment by influencing the trafficking and function of immune cells like Tregs and M2 macrophages.

Increasing the expression of PD-L1 on tumor cells, which is a key biomarker for responsiveness to checkpoint inhibitors.

These mechanisms could potentially broaden the applicability of checkpoint inhibitors to a wider range of solid tumor types, especially those that are initially "cold" and unresponsive to current immunotherapies.

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