Enrichment of Foxp3+ CD4 Regulatory T Cells in Migrated T Cells to IL-6– and IL-8–Expressing Tumors through Predominant Induction of CXCR1 by IL-6

Abstract Analysis of cytokine and chemokine production by tumor cell lines including five lung cancers, a malignant mesothelioma, and a malignant melanoma recently established in our laboratory showed rather high production of IL-8 in all tumors and IL-6 in one lung cancer, the malignant mesothelioma, and the malignant melanoma. We investigated the migration of PBMCs to these tumor cells using Transwell plates and showed enrichment of Foxp3+ CD4 regulatory T cells (Tregs) in migrated T cells to both IL-6– and IL-8–producing tumors. Marked induction of CXCR1 expression on Foxp3+ CD4 Tregs by IL-6 followed by IL-8–mediated migration appeared to be responsible for enriched migration. Frequent production of IL-8 by the tumors and Treg migration to those tumors through induction of IL-8R expression by IL-6 is one of the mechanisms for tumor escape.