Induction of IP-10/CXCL10 secretion as an immunomodulatory effect of low-dose adjuvant interferon-alpha during treatment of melanoma.
This study investigated the immunomodulatory effects of low-dose interferon-alpha (IFN-alpha) in a cohort of 21 stage II or III melanoma patients treated in an adjuvant setting. Serial assessments in peripheral blood were performed at baseline and at regular intervals. Depletion of CD3+CD4+ T cells was predominant within the "central memory" and "memory" subsets. The impact of IFN-alpha was more marked at the level of all CD3+CD8+ T-cell subsets that showed a sustained and significant decrease. Both myeloid and plasmacytoid dendritic cell (DC) subsets were depleted, but the MDC/PDC ratio tended to increase 12 months after treatment. Also, CD14+CD16+ monocytes showed a significant increase of both MHC class I and the CD86 costimulatory molecule. IP-10/CXCL10 plasma levels significantly increased already at 3 months of therapy and remained at significantly high levels during the study period. The dramatic increase of IP-10/CXCL10 inversely correlated with a significant decrease of the CXCR3+CD8+ T lymphocytes. Low-dose IFN-alpha therapy can significantly affect phenotypic and functional properties of blood circulating lymphocytes and antigen-presenting cells, and production of IP-10/CXCL10, that appear to be important for the orchestration of an effective immune response during adjuvant IFN-alpha therapy for melanoma.
Mohty
Anne-Marie
AM
Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Université de la Méditerranée, INSERM UMR 599, 232 Bd. Sainte Marguerite, Marseille Cedex 09, France.
Grob
Jean-Jacques
JJ
Mohty
Mohamad
M
Richard
Marie-Aleth
MA
Olive
Daniel
D
Gaugler
Béatrice
B
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000276:immunology; D054357:Chemokine CXCL10 / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005602:France; D006801:Humans; D056747:Immunomodulation; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D018655:Lymphocyte Count; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D054367:Receptors, CXCR3 / Q000276:immunology; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000276:Adjuvants, Immunologic; D017252:CD3 Complex; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D054367:Receptors, CXCR3; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b