A Ludwig Disease Exploration study has shown that a few particles recently used to treat hypertension could likewise assist the safe framework with bettering objective malignant growth cells. These findings, which were published in the most recent issue of Nature, have the potential to, over time, significantly enhance the usefulness and efficacy of cancer immunotherapy.
Benoît Van den Eynde, a member of the Ludwig Institute for Cancer Research, co-director of the de Duve Institute, and professor of tumor immunology at the University of Oxford, stated, “Immunotherapy can effectively fight only 30% to 40% of cancers today.” T lymphocytes that are not sufficiently reactive are a major reason why many cancers are resistant. We discovered that these kinds of cancers that are resistant to immunotherapy may benefit from medications that were once used to treat hypertension.
By eliminating foreign substances and pathogens like bacteria and viruses, the immune system fights disease. In this process, T lymphocytes, a type of white blood cell, play an active role. They perceive and obliterate cells that seem unfamiliar.
“Many cancers are resistant, owing to insufficiently reactive T lymphocytes. We observed that medications previously used to treat hypertension could have an intriguing effect in treating these immunotherapy-resistant tumors.”
Benoît Van den Eynde, who is a member of the Ludwig Institute for Cancer Research,
T lymphocytes, on the other hand, frequently fail to recognize and attack cancer cells because they are not foreign. However, around 30 years ago, Thierry Boon and his colleagues at the former Brussels Branch of the Ludwig Institute for Cancer Research at the de Duve Institute discovered tumor antigens, which are specific markers on the surface of cancer cells that T cells, which then destroy the cancerous cells, can recognize.
This research laid the groundwork for cancer immunotherapy, a treatment strategy in which T cells aid in the destruction of cancerous cells. Because of lymphocytes’ explicitness and memory of growth antigens, immunotherapy makes it conceivable to treat progressing diseases with some success. It is now utilized globally. However, not all patients or cancer types respond to these treatments in the same way.
In the current study, a group led by Jingjing Zhu in Van den Eynde’s lab demonstrates that anti-hypertensive drug molecules known as 2-adrenergic receptor (2AR) agonists also have an effect on the behavior of macrophages, which are white blood cells that ingest and digest pathogen debris like cancer cells, microbes, and foreign substances. In addition, macrophages present suspicious antigens to T cells in an effort to elicit an immune response while simultaneously performing that function.
Zhu, Van den Eynde, and colleagues discovered that in addition to their well-known hypotensive and anesthetic effects, 2AR agonists can also stimulate macrophages in their capacity as sentinels, thereby increasing the reactivity of T cells and increasing their effectiveness in rejecting cancer cells. The effect was especially noticeable in cancer models that were incapable of responding to standard immunotherapy. Even for the many kinds of cancer that don’t respond well to clinical immunotherapy, this suggests that the new strategy could improve its efficacy.
Additionally, these findings provide a justification for the creation of novel molecules that could be utilized in conjunction with immunotherapy to enhance its efficacy.
“One could envision utilizing existing pulses to bring down drugs,” said Van lair Eynde. ” However, that would be very unsafe, inferable from the undesired impacts and the poisonousness of these medications at the fundamental portions. A different strategy would be to create new molecules that would behave similarly to macrophages but would not cause harmful side effects. In this direction, we have already made significant progress.”
More information: Jingjing Zhu et al, Tumour immune rejection triggered by activation of α2-adrenergic receptors, Nature (2023). DOI: 10.1038/s41586-023-06110-8
