title: Dysregulated CC receptor/ligand in monocytes/macrophages from tongue squamous cell carcinoma patients is partially rectified by interferon α-2b.
abstract: In an aim to rectify dysregulated CC chemokine receptor (CCR5)/ligand (RANTES, MIP-1α, MIP-1β) status of monocytes/macrophages in tongue squamous cell carcinoma (TSCC; n = 12) patients, we have tested interferon α2b (IFNα2b), a novel immunomodulator with wide use in the management of several forms of cancer. IFNα2b can upregulate reduced CCR5 expression and increases the suppressed secretory status of its ligands, as evidenced from in vitro studies on monocytes/macrophages from the peripheral blood of TSCC patients as well as healthy individuals. Isolated monocytes of TSCC patients (n = 5) undergoing chemotherapeutic treatment along with IFNα2b immunotherapy demonstrated significant upregulation in CCR5 expression and secretion of corresponding ligands. These rectifications in receptor/ligand levels are reflected in improved CCR5-dependent migration of monocytes/macrophages after IFNα2b treatment. The rectified chemokine profile and cellular migration translate into better tumoricidal and antigen-presenting functions of these cells. Accordingly, enhanced T-cell-mediated tumor cell killing is demonstrated upon IFNα2b treatment. Translating dual benefits on monocyte/macrophage functions, IFNα2b may emerge as a potential form of immunotherapy for TSCC patients that may be combined with standard chemotherapy for better clinical outcome.
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Chakraborty
authors.forename: Anamika
authors.initials: A
authors.lastname: Bose
authors.forename: Kuntal K
authors.initials: KK
authors.lastname: Goswami
authors.forename: Kalyan K
authors.initials: KK
authors.lastname: Mukherjee
authors.forename: Shyamal
authors.initials: S
authors.lastname: Goswami
authors.forename: Diptendu
authors.initials: D
authors.lastname: Ghosh
authors.forename: Tathagata
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Koustav
authors.initials: K
authors.lastname: Sarkar
authors.forename: Smarajit
authors.initials: S
authors.lastname: Pal
authors.forename: Anup
authors.initials: A
authors.lastname: Bhowmick
authors.forename: Jaydip
authors.initials: J
authors.lastname: Biswas
authors.forename: Rathindranath
authors.initials: R
authors.lastname: Baral
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000276:immunology / Q000378:metabolism*; D054407:Chemokine CCL4 / Q000276:immunology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D008024:Ligands; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D020298:U937 Cells
chemical_list: C066507:CCL4 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008024:Ligands; D019713:Receptors, CCR5; D011994:Recombinant Proteins