Multiscale modeling reveals synergy between CCL19 and PD-1 blockade in reshaping the TNBC microenvironment
Year: 2026
Type: article
Abstract: Triple-negative breast cancer (TNBC) presents a major clinical challenge owing to its immunosuppressive tumor microenvironment, target scarcity, and poor therapeutic response. Recently, the combination therapy of immune checkpoint blockade and CCL19 has shown significant efficacy in TNBC. To systematically unravel the synergistic mechanisms between CCL19 and anti-PD-1, we developed a mathematical model by integrating cellular and molecular scales to capture essential tumor-immune interactions and predict the dynamics of tumor evolution under various therapies. In this study, we proposed three quantitative indicators: (1) the tumor relative volume index (TRVI), (2) the therapeutic efficacy discrepancy index (TEDI), and (3) the immune heterogeneity treatment response index (IHTRI). Our model validated that the immunostimulatory effect of CCL19 in synergizing with anti-PD-1, and revealed that this synergy is highly modulated by individual baseline immune heterogeneity. Notably, our analysis identified (CTLs × CCL19)/PD-L1 as a novel dynamic biomarker combination with significant predictive (AUC = 0.86) and prognostic value (log-rank p= 0.019). Finally, virtual clinical trials revealed that administering anti-PD-1 therapy prior to CCL19 injection draws more significant clinical benefits in TNBC. Collectively, this study provides a theoretical foundation for elucidating the synergistic mechanism between CCL19-mediated immunostimulation and anti-PD-1 therapy.
Authors: Chunjie Gao, Chenghang Li, Lei Du, Jing Liu, Jinzhi Lei, Lei Wang
Institutions: Xinjiang Medical University, Tiangong University
Language: English
Subfield: Modeling and Simulation
Field: Mathematics
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,490
Awards: G4737497079, 新疆结核病耐药发展机制的动力学建模与分析
OpenAlex ID: W7154589673