Interferon alpha2b augments suppressed immune functions in tobacco-related head and neck squamous cell carcinoma patients by modulating cytokine signaling.
We have examined the role of interferon alpha2b (IFNalpha2b) in augmentation of the suppressed immune functions and cytotoxicity of tobacco-related head and neck squamous cell carcinoma (HNSCC) patients. The suppressed killing activity of PBMC of HNSCC patients towards KB, MCF7 and K562 cell lines could be restored by in vitro treatment of PBMC with IFNalpha2b, as detected by LDH release assay. HNSCC patients with cisplatin + 5FU + IFNalpha2b treatment showed greater cytotoxic efficacy than corresponding pretreatment values. Analysis of culture supernatant of HNSCC-PBMC by ELISA revealed the lower secretion of IL-12 and IFNgamma with increased level of IL-4 and IL-10. This altered Th1/Th2 status was rectified after in vitro and in vivo IFNalpha2b stimulation. Increased secretion of monocyte derived IL-12 was observed after IFNalpha2b treatment that can enhance the IFNgamma release, a key regulator for cytotoxicity. IFNalpha2b stimulated enhancement of NK cells may be the source of greater amount of IFNgamma. IFNalpha2b activated STAT1 and STAT4 signaling is observed to be involved in the regulation and maintenance of cytokine milieu. We conclude that IFNalpha2b may be effective as a tool for adjuvant therapy along with conventional therapies to overcome the immunosuppression in HNSCC patients.
Bose
Anamika
A
Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, 37 S.P. Mookherjee Road, Kolkata, West Bengal 700026, India.
Ghosh
Diptendu
D
Pal
Smarajit
S
Mukherjee
Kalyan K
KK
Biswas
Jaydip
J
Baral
Rathindranath
R
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D018655:Lymphocyte Count; D008262:Macrophage Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014029:Tobacco Use Disorder / Q000150:complications / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins