Abstract LB403: Mechanisms of tumor dormancy through immune niche formation, and its impact on immune therapeutic relapse

Abstract Residual breast cancer cells can persist in a dormant state during prolonged clinical remissions, yet immune regulated mechanisms that actively maintain dormancy or permit metastatic reactivation remain poorly understood. Defining these mechanisms is critical to preventing late relapse following systemic therapy and immunotherapy. Here, we identify a myeloid driven immune-tumor circuit that enforces breast cancer dormancy and represents a therapeutically actionable vulnerability. Genetic abrogation of myeloid TGF-β receptor II generated an IFN-γ rich tumor microenvironment that induced durable quiescence of breast cancer cells. IFN-γ signaling activated a KLF4 dependent transcriptional program in malignant cells, leading to induction of SLURP1, which enforced dormancy by disrupting fibronectin-integrin signaling required for proliferative outgrowth. Dormant breast cancer lesions localized to spatially restricted immune niches enriched for NK cells, conventional dendritic cells, monocytes, and neutrophils. Despite this immune infiltration, dormant tumor cells evaded NK cell mediated elimination through engagement of the CD200-CD200R1 inhibitory axis. Therapeutically, disruption of CD200-mediated immune suppression reactivated immune surveillance and, when combined with chemotherapy and immune checkpoint blockade, resulted in robust eradication of dormant breast cancer cells.Collectively, these findings define the IFN-γ-KLF4-SLURP1 and CD200-CD200R1 axis as critical regulators of immune-enforced breast cancer dormancy and establish a late-breaking combinatorial strategy to eliminate dormant disease and prevent relapse following immunotherapy. Citation Format: Abdul Ahad, Jae Young So, Hiroshi Ichise, Edward Schrom, Carter Sellner, Yang Gu, Woo Yong Park, Ronald N. Germain, Li Yang. Mechanisms of tumor dormancy through immune niche formation, and its impact on immune therapeutic relapse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB403.