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Dysregulated CC receptor/ligand in monocytes/macrophages from tongue squamous cell carcinoma patients is partially
Krishnendu Chakraborty1, Anamika Bose, Kuntal K Goswami
1Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.
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.
Insights
Interferon alfa-2b (IFNα2b) therapy can restore CC chemokine receptor 5 (CCR5) and ligand levels in tongue squamous cell carcinoma (TSCC) patients. This immunotherapy enhances monocyte/macrophage functions, improving T-cell-mediated tumor killing.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Dysregulated CC chemokine receptor 5 (CCR5) and its ligands (RANTES, MIP-1α, MIP-1β) are observed in monocytes/macrophages of tongue squamous cell carcinoma (TSCC) patients.
- This dysregulation impacts immune cell function and potentially tumor progression.
Purpose of the Study:
- To investigate the potential of interferon alfa-2b (IFNα2b) as an immunomodulator to rectify CCR5/ligand dysregulation in TSCC.
- To assess the effects of IFNα2b on monocyte/macrophage function, including migration, tumoricidal activity, and antigen presentation.
Main Methods:
- In vitro studies on monocytes/macrophages isolated from peripheral blood of TSCC patients and healthy individuals.
- Treatment of TSCC patient monocytes with IFNα2b, alone and in combination with chemotherapy.
- Assessment of CCR5 expression, ligand secretion, cell migration, and T-cell-mediated tumor cell killing.
Main Results:
- IFNα2b significantly upregulated CCR5 expression and increased the secretion of its ligands in monocytes/macrophages from TSCC patients.
- IFNα2b treatment improved CCR5-dependent monocyte/macrophage migration.
- Enhanced tumoricidal and antigen-presenting functions of monocytes/macrophages were observed, leading to improved T-cell-mediated tumor cell killing.
Conclusions:
- IFNα2b demonstrates potential as an immunomodulatory agent to correct chemokine imbalances in TSCC.
- IFNα2b may enhance anti-tumor immunity by improving monocyte/macrophage functions.
- Combination therapy of IFNα2b with standard chemotherapy could offer improved clinical outcomes for TSCC patients.
