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.
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.
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Japan.
Shingo
S
Eikawa
Yoshihiro
Y
Ohue
Kenta
K
Kitaoka
Toshiki
T
Aji
Akiko
A
Uenaka
Mikio
M
Oka
Eiichi
E
Nakayama
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000502:physiology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000502:physiology; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D008654:Mesothelioma / Q000276:immunology / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis* / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000276:immunology
C508606:CXCL8 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A