Background 

Bladder cancer is one of the most difficult cancers to treat, especially once it spreads to other parts of the body. Doctors sometimes use a treatment called immunotherapy, which helps the body’s own immune system fight the cancer. While this treatment can work very well for some patients, most people with advanced bladder cancer do not respond as strongly. Scientists are trying to understand why some tumors resist immunotherapy so they can help more patients benefit from it. 

In this study, researchers found that tumors resistant to immunotherapy have a special “signature” in their genes that suggests harmful inflammation—similar to what happens in infections. They discovered that a certain type of immune cell, called an SPP1+ macrophage, may be responsible for this harmful inflammation. These cells show high levels of a gene called TREM1, which is already known to cause damaging inflammation in diseases outside of cancer. 

What the Study Proposes to Address 

The research team believes that SPP1+ macrophages are key players in making some bladder cancers resistant to immunotherapy. They think that blocking the activity of TREM1 could help the immune system fight cancer more effectively. To explore this, the team will closely study tumor samples from bladder cancer patients who have received immunotherapy. Using advanced imaging and genetic testing, they will look at how these macrophages interact with other cells inside the tumor. 

The researchers will also use novel drugs designed to block TREM1, which they believe might help overcome resistance to immunotherapy in bladder cancer. 

Why This Research is Important 

For people with advanced bladder cancer, current treatments often stop working, leaving few options. This research could change that. By learning how SPP1+ macrophages and TREM1 make tumors resistant to immunotherapy, scientists may uncover a new way to make this treatment more effective for more patients. 

If successful, the study could lead to new treatments that directly target TREM1 and the immune cells driving resistance. This could help many more bladder cancer patients live longer, healthier lives. The study represents an important step toward personalizing care and improving outcomes for those facing advanced bladder cancer. 

Final Report Summary

This research focuses on a type of immune cell called SPP1+ macrophages found inside bladder tumors. Researchers used advanced imaging tools to study tumor samples from patients who received immunotherapy. They found that SPP1+ macrophages tend to live in areas of the tumor with very little oxygen and few immune cells that can fight cancer. Another group of macrophages, which are linked to better responses to immunotherapy, were found in different areas of the tumor—closer to other immune cells that help attack cancer. 

To learn more about SPP1+ macrophages, the team created a laboratory model that accurately reproduces how these cells behave in the body. They tested this model in several ways, including studying the genes these cells use and seeing how they affect other immune cells. The results showed that SPP1+ macrophages can block other immune cells from killing cancer cells. 

The researchers also discovered that these macrophages have high activity of a gene called TREM1. This finding is helping them test new drugs that can block TREM1 and possibly remove the barriers that prevent immunotherapy from working well for people with bladder cancer. 

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None Reported as of August 2025

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