Cancer sometimes gets the immune system to back off. A new study shows that a natural signal, a hormone, can tell certain white blood cells to slow down, which lets tumors grow.
This finding points to a fresh target for treatment. It also helps explain why powerful cancer drugs work well for some people but not for others.
Why this study matters
The work was co-led by Cheng Cheng “Alec” Zhang, Ph.D., Professor of Physiology at UT Southwestern Medical Center.
Across common cancers like lung, kidney, and melanoma, only about 20 to 30 percent of patients benefit from these drugs called immune checkpoint inhibitors – medicines that remove natural brakes on T-cells so those cells attack tumors more strongly.
They help many people but not all. That leaves a lot of patients needing new options.
Many tumors build up cells from a group called myeloid cells, early responder white blood cells that usually help start immune defense. These cells can turn suppressive in cancer and hold back T-cells.
Cancer also changes the immune system beyond the tumor site. That broader shift matters for whether treatments work, a 2021 review explains.
Study focuses on SCG2
The team focused on secretogranin 2 (SCG2) which acts like a hormone – a chemical messenger that cells release to send signals through the body.
They discovered that SCG2 latches onto LILRB4, a receptor, which is a docking site on the surface of certain myeloid cells that catches a signal like a hormone.
When SCG2 binds LILRB4, it tells those cells to ease off their tumor fighting jobs. It also interferes with the call for backup from T-cells.
Inside these cells, the signal turns on STAT3, a protein that switches many genes on or off. When STAT3 is active in myeloid cells, those cells tend to suppress other immune cells.
The result is a one two punch. The early responders stop helping, and the later responders do not get to the tumor in normal numbers.
How the tests were done
The researchers first confirmed the SCG2 to LILRB4 match in dishes of cells. They showed that the binding turned down myeloid cell activity that would otherwise help fight tumors.
They then used mice whose myeloid cells carried the human form of LILRB4. Tumors that produced SCG2 grew faster in those mice, while blocking LILRB4 slowed growth, and removing SCG2 also slowed growth.
The team also showed that the growth boost from SCG2 depended on T-cells. When T-cells were taken out of the picture, the advantage went away.
“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. Our study suggests that receptors on these myeloid cells get stimulated by this hormone and end up suppressing the immune system,” said Zhang.
What it could mean for care
Blocking LILRB4 could become a new way to help more patients respond to treatment. It makes sense to test LILRB4 blockers with existing checkpoint drugs in careful trials.
There is early support for targeting this receptor from other diseases. In multiple myeloma, blocking LILRB4 slowed disease growth in lab and animal tests.
The pathway also leans on STAT3, which is a central control switch in these suppressive cells. A 2025 review notes that STAT3 helps these cells grow and shut down T-cells, so pairing a LILRB4 blocker with a STAT3 focused drug might be useful.
There is another angle too. Because SCG2 can quiet myeloid cells, carefully adding SCG2 might one day help calm certain inflammatory conditions that run too hot.
Questions people may ask
Can doctors measure SCG2 in blood or tumor tissue to guide care. That will require tests that are accurate and easy to run in clinics.
Will blocking LILRB4 cause infections or other issues since the receptor helps keep inflammation in check. Safety will need close monitoring in early trials.
Could tumors switch to a different signal if LILRB4 is blocked. Cancers often adapt, so combinations may be important.
How would doctors choose who gets a LILRB4 blocker. Matching the drug to tumors that use the SCG2 to LILRB4 route will likely matter.
Where research goes next
Build a reliable test for SCG2 levels and LILRB4 activity. Use it to pick patients who are most likely to benefit.
Run trials that add LILRB4 blockers to checkpoint therapy. Track whether more patients respond and how long responses last.
Map this pathway in different cancers and in human samples over time. Learn when the pathway turns on and how best to shut it off.
Study whether carefully giving SCG2 can help dial down harmful inflammation in certain diseases. Keep a close eye on side effects while doing so.
The study is published in Nature Immunology.
—–
Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates.
Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.
—–