What is it about?
Scientists recognize that for cancer to exist, tumors must devise methods to avoid detection by the immune system. One such method that cancers use is the recruitment of regulatory T cells (Tregs), a population of white blood cells that normally prevent your immune system from attacking healthy self-tissues. Prior studies have shown that eliminating Tregs dramatically improves cancer outcomes in preclinical mouse models; however, this treatment also results in lethal autoimmunity and thus this technique is not suitable for clinical use. We have now discovered that eliminating a subset of Tregs, called peripheral-derived Tregs (pTregs), improves cancer outcomes in preclinical mouse models without contributing to autoimmunity. In the absence of pTregs, cancers cannot establish an immune-suppressive environment, which allows the host immune system to safely prevent/delay tumors from reaching a malignant stage.
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Why is it important?
Cancers need to shut down anti-tumor immunity for these transformed cells to exist and conversely, reviving anti-tumor immunity in cancer patients can dramatically improve disease outcomes. Cancer treatments that target the host immune system have significant advantages over conventional therapies, including a lack of selective pressure for tumor mutation/escape and potential universality of action. Unfortunately, the same suppressive events that allowed tumors to originally escape immune detection can impair immune-based treatments, rendering them ineffective. We have discovered that cancers use pTregs to initially establish an immune-suppressive environment and that blocking the generation of pTregs safely prevents/delays tumor progression. Therefore, it appears that pTregs are a viable target for cancer treatment, either alone or in concert with other established therapies that revive anti-tumor immune responses.
Perspectives
I hope that the readership will appreciate the time and effort that went into many of these experiments. For instance, the data showing that mice with spontaneous prostate cancer survive to a much greater extent if they lack pTregs took about 4 years to acquire. It's a single frame in a multi-figure paper, but I'm very proud of the achievement.
Eric Sebzda
Wayne State University
Read the Original
This page is a summary of: Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a nonredundant manner, Proceedings of the National Academy of Sciences, August 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2404916121.
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