Triple negative breast cancer (TNBC) is an aggressive subtype devoid of targeted therapies, making immunotherapy a promising but unpredictable option. Current biomarkers, such as the expression of PD-L1 or the tumor mutational charge, often do not reliably predict the success of treatment due to the complexity of immune responses. In addition, invasive tumor biopsies are not practical for frequent monitoring. The plasma proteomics, which analyzes blood proteins, offers a non-invasive alternative but remains under-explored in the TNBC. Previous studies have linked certain plasma proteins to immune activity, but none have systematically mapped their dynamics during immunotherapy or linked them to clinical results. Based on these challenges, there is an urgent need to identify reliable and non -invasive biomarkers to optimize immunotherapy for TNBC patients.
Published (DOI: 10.20892 / J.issn.2095-3941.2025.0038) on July 4, 2025, in Biology and cancer medicineResearchers from the Fudan University Shanghai Cancer Center and the Shanghai Institute for Biomedical and Pharmaceutical Technologies have unveiled a 195 TNBC patient study. Using high sensitivity tests, the team followed 92 immune proteins before, during and after immunotherapy. They identified ARG1, Nos3 et CD28 As key response predictors and developed pipscore, a model with an accuracy of 85.8%. The study includes unique RNA sequencing to correlate blood results with changes in tumor microenvironment, offering a holistic vision of immunotherapy dynamics.
The study revealed spectacular changes in plasma protein rates after immunotherapy, with immune active proteins like CXCL9 and IFN-γ increasing in responders. In particular, patients reaching a complete pathological response (PCR) had higher arg1 and CD28 levels but higher NOS3 levels, suggesting that these proteins regulate immune activation and the suppression of tumors. PipScore, combining six proteins (for example, ARG1, NOS3, IL-18), has laminate patients in high and low response groups with striking precision (AUC 0.858). High pipecors were correlated with better results, while weak scores indicated resistance. Cell RNA sequencing is still linked plasma proteins to tumor microenvironment changes. For example, high levels of NOS3 associated with fewer CD8 + T cells in tumors, referring to immunosuppressive effects. Vice versa, ARG1The role of arginine metabolism can improve the function of T cells. The team has validated the results via Elisa, confirming the reliability of their proteomic platform. An out -of -competition point was the prognostic power of pipscore: it predicted survival without progression of 12 months with 96%precision. This tool could rationalize clinical decision -making, identifying the ideal candidates for immunotherapy in advance.
This study transforms the way we approach TNBC immunotherapy. By translating the proteomics of complex plasma into a practical score, we have filled the gap between research and clinical utility. PipScore predicts not only the answer, but also opens the doors to target metabolic pathways such as arginine deprivation to overcome resistance. These results emphasize that systemic immunity, not just tumor microenvironment, dictates the success of treatment. “”
Dr Yizhou Jiang, author of Co-Corréide
PipScore could soon guide oncologists in the selection of TNBC patients for immunotherapy, reducing unnecessary secondary effects and costs. Its non -invasive nature allows repeated monitoring, allowing real -time adjustments to treatment plans. Beyond TNBC, this approach could apply to other cancers where the effectiveness of immunotherapy varies considerably.
