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Researchers at UT Southwestern Medical Center have uncovered a novel mechanism by which cancer cells avoid detection and destruction by the body’s own immune system, potentially paving the way for next-generation immunotherapies.
In a recent study published in Nature Immunology, the team led by Dr. Cheng Cheng “Alec” Zhang and Dr. Xing Yang discovered that a hormone called secretogranin 2 (SCG2) binds to a specific receptor—LILRB4—on the surface of myeloid immune cells. This interaction effectively shuts down the immune cells’ tumor-fighting capabilities, allowing cancer cells to grow unchecked and evade the immune response.
“Myeloid cells are among the first group of immune cells recruited to tumors, but very quickly these tumor-fighting cells turn into tumor-supporting cells,” said Dr. Zhang. “Our study suggests that receptors on these myeloid cells get stimulated by this hormone and end up suppressing the immune system.”
Unlocking a New Target for Cancer Immunotherapy
The breakthrough stems from previous findings that myeloid cells, typically tasked with attacking tumors, instead lose their potency after cancer takes root. Researchers identified the inhibitory receptor LILRB4 on these cells and conducted a genome-wide screen to find potential binders. SCG2—whose immune function had been obscure—emerged as a top candidate.
Laboratory experiments confirmed that SCG2’s binding to LILRB4 sets off a signaling cascade that not only neutralizes the myeloid cells’ anti-tumor abilities but also prevents them from recruiting vital T cells to the tumor microenvironment.
In mouse models genetically engineered to express the human version of LILRB4, cancers producing SCG2 rapidly established tumors. However, blocking LILRB4 with a specialized antibody or depleting SCG2 from the system substantially slowed tumor growth.
Implications: Double-Edged Sword
This discovery reveals a new explanation for why current immunotherapies, such as immune checkpoint inhibitors, only benefit about 20–30% of cancer patients. By targeting the SCG2-LILRB4 interaction, researchers hope to broaden the effectiveness of immunotherapy for a larger group of patients.
Interestingly, the research also hints at applications beyond oncology. Since the SCG2-LILRB4 axis can suppress immune cell activity, boosting SCG2 levels might offer a therapeutic strategy for autoimmune and inflammatory diseases in which myeloid cells are overly active.
“Disrupting this interaction could someday offer a new immunotherapy option to treat cancer,” Dr. Zhang stated, noting that further studies are planned to explore both cancer and autoimmune applications.
Disclaimer:
This article summarizes recently published scientific research and is intended for informational purposes only. The findings described are at the experimental stage and have not yet been approved or implemented in clinical treatments. If you have questions about cancer therapies or your health, please consult with a qualified medical professional for personalized advice.
