Mayo Clinic Breakthrough: Targeting Myeloid Cells to Supercharge Cancer Immunotherapy
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A new understanding of immune cell interactions is poised to enhance the effectiveness of cancer treatments, offering hope for patients facing immunotherapy resistance.
researchers at the Mayo Clinic have pinpointed a specific type of immune cell – the myeloid cell – as key to boosting the power of T cells, the immune system’s primary cancer fighters. Two independent research teams, employing different methodologies, converged on the same conclusion: manipulating myeloid cells can significantly enhance the activity of T cells, the immune system’s primary cancer fighters.
This finding suggests a potential pathway to overcome limitations in current immune checkpoint therapies, which, while effective for some cancers, often fail to provide lasting remission. A phase 1 clinical trial to test these enhanced cells in patients is currently in advancement at the Mayo Clinic.
Unlocking T Cell potential by Targeting PD-L1 Recycling
One research team, publishing their findings in the Journal for ImmunoTherapy of Cancer, focused on overcoming the limitations of treatments targeting the proteins PD-1 and PD-L1. these proteins suppress the ability of T cells to attack cancer. While existing immunotherapies aim to block PD-L1, researchers discovered a natural “recycling process” allows the molecule to persist and continue suppressing immune response.
“Our study found the importance of the recycling process, and we present a way to address it,” explained a senior researcher involved in the study.
To combat this, the team developed an antibody, designated H1A, capable of reducing PD-L1 levels in human myeloid cells and preventing its recycling. by blocking this process, the myeloid cells were able to more effectively activate cancer-killing T cells.
“We now have a tool that can completely remove PD-L1 and in doing so we have more myeloid cell activation,” stated the study’s lead author. “Identifying the myeloid cell was an unexpected discovery,” she added, highlighting the serendipitous nature of the breakthrough.
Macrophages: Unexpected Allies in the Fight Against Cancer
A second Mayo Clinic team, led by researchers in Arizona and reporting in iScience, arrived at a similar conclusion through a different approach. Utilizing live-cell microscopy, they observed that macrophages – a specific type of myeloid cell – play a crucial role in activating T cells.
In mouse models, the team found that T cells interact closely with macrophages, creating a molecular habitat conducive to tumor cell destruction. This finding represents a significant shift in understanding how immunotherapy functions.
“This is a paradigm shift for PD-L1 immunotherapy, which has traditionally focused on the interaction of the tumor and the T cells,” said a lead immunology researcher. “We found that it’s vital to co-opt the macrophage, which acts as another immune cell partner.”
Further research revealed the potential to “reprogram” tumor macrophages, making them more pro-inflammatory and enhancing their ability to activate T cells. “We can directly reprogram tumor macrophages to be more pro-inflammatory. They can become better T-cell activators and drive better tumor control. reprogramming of the macrophage may be key to being able to prevent therapy resistance and change outcomes for patients,” explained a lead author of the iScience study.
Clinical Trials and Future Implications
Based on the converging findings from both laboratories, a phase 1 clinical trial evaluating the antibody H1A is now being planned. This research holds the promise of not only improving the efficacy of existing immunotherapies but also addressing the critical issue of therapy resistance and expanding treatment options for a wider range of cancer patients.
For a complete list of authors, disclosures, and funding information, please review the studies in Journal for ImmunoTherapy of cancer and iScience.
