A groundbreaking study has discovered a way to predict whether patients with triple-negative breast cancer (TNBC) will respond well to immunotherapy—using just a blood test.
Researchers have identified specific proteins in the blood that are strongly linked to how patients react to treatment. These proteins include ARG1, NOS3, and CD28.
Using this information, the scientists created a scoring system called the Plasma Immuno Prediction Score, or PIPscore, which can accurately forecast treatment outcomes.
This non-invasive test could help doctors create more personalized treatment plans and avoid giving ineffective therapy to patients who won’t benefit from it.
TNBC is one of the most aggressive and hard-to-treat types of breast cancer. Unlike other breast cancers, TNBC doesn’t have hormone or HER2 receptors, which means common targeted treatments don’t work. Immunotherapy has shown promise, but not all patients respond well, and it’s difficult to know in advance who will benefit.
Current tools like PD-L1 testing or tumor genetic testing aren’t always reliable. Plus, getting tumor tissue samples through biopsies is invasive and not always practical to repeat. That’s why this new study focused on blood-based proteins as a safer and easier option.
The research was published on July 4, 2025, in the journal Cancer Biology & Medicine. Scientists from Fudan University Shanghai Cancer Center and the Shanghai Institute for Biomedical and Pharmaceutical Technologies led the study.
They studied blood samples from 195 patients with TNBC, using highly sensitive tests to look at 92 proteins involved in the immune system. They collected samples before, during, and after the patients received immunotherapy.
The results were striking. Some proteins clearly changed in people who responded well to treatment. For instance, proteins that help activate the immune system, like CXCL9 and IFN-γ, increased in those who got better.
Patients who reached what doctors call a “pathologic complete response,” meaning no cancer was found after treatment, had higher levels of ARG1 and CD28 but lower levels of NOS3. This suggests that these proteins play key roles in either helping or blocking the immune system’s ability to fight cancer.
To make these findings more useful for real-world care, the researchers created the PIPscore. This score combines six important proteins, including ARG1, NOS3, and IL-18, into one easy-to-use number.
A high PIPscore means a patient is more likely to benefit from immunotherapy, while a low score means the treatment might not work. The model was able to sort patients with about 86% accuracy and even predicted 12-month progression-free survival with 96% accuracy.
The team also used single-cell RNA sequencing to see how the blood protein changes related to what was happening inside the tumors. For example, when NOS3 levels were high, there were fewer of the cancer-fighting CD8+ T cells inside tumors, showing a possible link to weaker immune responses.
In contrast, ARG1 may improve how T cells work by changing arginine levels in the body. These links between blood and tumor changes offer a complete picture of how the immune system reacts to treatment.
Dr. Yizhou Jiang, one of the lead researchers, said, “This study transforms how we approach TNBC immunotherapy. By turning complex lab results into a simple score, we’ve created a tool that can actually help doctors make better decisions.
It also shows us new ways to improve treatment, like targeting metabolic pathways to help the immune system fight better.”
In the future, the PIPscore could be used in clinics to decide which TNBC patients should get immunotherapy. Since it only requires a blood test, doctors could check patients multiple times to see how they’re responding and adjust treatment if needed.
This could save time, reduce side effects, and avoid wasting resources. The approach may also work for other types of cancer where immunotherapy works for some people but not others.
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The study is published in Cancer Biology & Medicine.
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