Interferon α2b augments suppressed immune functions in tobacco-related head and neck squamous cell carcinoma patients by modulating cytokine signaling

SummaryWe have examined the role of interferon α2b (IFNα2b) 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 IFNα2b, as detected by LDH release assay. HNSCC patients with cisplatin + 5FU + IFNα2b 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 IFNγ with increased level of IL-4 and IL-10. This altered Th1/Th2 status was rectified after in vitro and in vivo IFNα2b stimulation. Increased secretion of monocyte derived IL-12 was observed after IFNα2b treatment that can enhance the IFNγ release, a key regulator for cytotoxicity. IFNα2b stimulated enhancement of NK cells may be the source of greater amount of IFNγ. IFNα2b activated STAT1 and STAT4 signaling is observed to be involved in the regulation and maintenance of cytokine milieu. We conclude that IFNα2b may be effective as a tool for adjuvant therapy along with conventional therapies to overcome the immunosuppression in HNSCC patients.