Researchers from the Fralin Biomedical Research Institute (Virginia Tech) Cancer Research Center in Washington, DC, have identified a group of cells called macrophages that, instead of protecting the body, appear to shield tumors from attack and promote tumor metastasis.1
Led by Shenglin Mei, PhD, the study focused on tumor-associated macrophages in advanced prostate cancer.
Dr Mei’s lab combined advanced techniques—including single-cell RNA sequencing, spatial transcriptomics, and NanoString digital spatial profiling—to map immune cell activity and location.
They also analyzed large-scale, publicly available datasets from hundreds of prostate cancer patients, ensuring their findings held up across human samples, mouse models, and disease stages.
Among 4 macrophage subtypes identified, one stood out: a group marked by the proteins SPP1 and TREM2. These cells were found clustered inside tumor regions—not in surrounding tissue—and were linked to blood vessel growth, impaired immune activity, and the spread of cancer in the body.
Using spatial analysis, the researchers concluded that inflammatory, potentially tumor-fighting macrophages tended to remain outside tumor boundaries, but a specific subtype that produces the troublesome SPP1 and TREM2 proteins was found deep inside the tumors, in close contact with cancer cells.
In follow-up experiments, Mei and colleagues tested whether blocking these cells could improve treatment. In mice with prostate tumors, they used an antibody to block the SPP1 protein—and noted that tumors were more vulnerable to immunotherapy.
Although immune checkpoint inhibitors have worked in many other cancers, they have failed in prostate cancer. However, in this study, combining anti-SPP1 treatment with immunotherapy significantly boosted the immune response.
“Targeting SPP1/TREM2 tumor-associated macrophages reversed immunosuppression, allowing more T cells—the immune system’s primary defenders—to infiltrate the tumor, resulting in slowed cancer progression,” Dr Mei said.
Prostate cancer is the second most commonly diagnosed cancer in men in the United States and globally, with an estimated 1.47 million new cases worldwide in 2022, according to the World Cancer Research Fund.
The research is the product of a multi-institutional collaboration that included Virginia Tech, Harvard Medical School, Massachusetts General Hospital, the University of Chicago, and Sweden’s Karolinska Institute.
References
- Mei S, Zhang H, Hirz T, et al. Single-cell and spatial transcriptomics reveal a tumor-associated macrophage subpopulation that mediates prostate cancer progression and metastasis. Mol Cancer Res. 2025;23:653-665.
- Pastor J. Scientists uncover immune cells that help prostate cancer resist treatment and a way to stop them. July 10, 2025. Accessed August 15, 2025. https://news.vt.edu/articles/2025/07/research-fralinbiomed-prostatecancer.html