Abstract PS3-13-01: Cik cell therapy remodels the immune microenvironment and suppresses cutaneous metastatic breast cancer in preclinical models

Abstract Background: Cutaneous metastases in breast cancer (CMBC) are clinically challenging and associated with poor prognosis and limited therapeutic options. Conventional treatments offer minimal survival benefit and often fail to control skin lesions. Emerging data suggest that immunotherapy, particularly adoptive cell therapy, may offer therapeutic promise. This study evaluates the feasibility and immunologic impact of cytokine-induced killer (CIK) cells in preclinical models of CMBC. Methods: We established in vitro and in vivo models using murine breast cancer cells with cutaneous metastatic potential. CIK cells were generated from peripheral blood mononuclear cells of murine splenocytes. Cytotoxicity assays, flow cytometry, transcriptomic profiling, and immunohistochemistry were used to assess anti-tumor effects and immune-related changes. The impact of CIK therapy alone or in combination with a TLR7 agonist was also examined. Results: Transcriptomic analysis of cutaneous lesions revealed upregulation of immune effector molecules (CXCL9/10/11, B2M, CD27) and checkpoint pathways (PD-L1). CMBC cells showed heightened sensitivity to CIK-mediated cytotoxicity compared to non-cutaneous metastatic cells. In vivo, CIK therapy significantly reduced cutaneous tumor burden and prolonged survival. Co-administration of a TLR7 agonist enhanced tumor cell apoptosis, reduced PD-L1 expression, and increased T-cell infiltration, suggesting a synergistic immunomodulatory effect. Conclusions: CIK cell therapy demonstrates strong preclinical efficacy against breast cancer cutaneous metastases and reshapes the tumor immune microenvironment. These findings support further development of CIK-based immunotherapy, potentially in combination with innate immune modulators, for patients with CMBC—a clinical subgroup with high unmet need. Citation Format: M. Hou, S. Chang, F. Chen, M. Pan, C. Luo. Cik cell therapy remodels the immune microenvironment and suppresses cutaneous metastatic breast cancer in preclinical models [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-01.