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Restoration of dysregulated CC chemokine signaling for monocyte/macrophage chemotaxis in head and neck squamous cell carcinoma patients by neem leaf glycoprotein maximizes tumor cell cytotoxicity

Cellular & Molecular Immunology volume 7, pages 396–408 (2010)Cite this article

Abstract

Previous studies have shown that the CC chemokine receptor CCR5 is downregulated on monocyte/macrophage (MO/Mφ) surfaces in head and neck squamous cell carcinoma (HNSCC) patients (stage IIIB). Ligands (RANTES, MIP-1α and MIP-1β) of this chemokine receptor were also secreted in lesser quantity from MO/Mφ of HNSCC patients in comparison with healthy individuals. In an aim to restore this dysregulated receptor–ligand signaling, we have used neem leaf glycoprotein (NLGP), a novel immunomodulator reported from our laboratory. NLGP upregulated CCR5 expression, as evidenced from studies on MO/Mφ of peripheral blood from HNSCC patients as well as healthy individuals. Expression of RANTES, MIP-1α and MIP-1β was also upregulated following NLGP treatment of these cells in vitro. Interestingly, NLGP has little effect on the expression of CCR5 and the ligand RANTES in oral cancer cells. This restored CCR5 receptor–ligand signaling seen in MO/Mφ was reflected in improved CCR5-dependent, p38 mitogen-activated protein kinase (MAPK)-mediated migration of MO/Mφ after NLGP treatment to a standard chemoattractant. NLGP also induces better antigen presentation and simultaneous costimulation to effector T cells by MO/Mφ by upregulating human leucocyte antigen (HLA)-ABC, CD80 and CD86. In addition, NLGP-treated MO/Mφ-primed T cells can effectively lyse tumor cells in vitro. The effects of NLGP on monocyte migration and T cell-mediated oral tumor cell killing were further demonstrated in transwell assays with or without CCR5 neutralization. These results suggest a new approach in cancer immunotherapy by modulating dysregulated CCR5 signals from MO/Mφ.

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Acknowledgements

Partial grant supports from the Indian Council of Medical Research, New Delhi (Grant Nos. 3/2/2/131/2007/NCD-III and Immuno/18/11/08/2006-ECD-I) and University Grant Commission, New Delhi (Grant No. F.2-3/2000 (SA-1) to AB and TC) are acknowledged. The authors thank Dr Jaydip Biswas, Director, CNCI, India, for providing necessary facilities. They also thank Dr Subrata Laskar, University of Burdwan, West Bengal, India, for his help in characterization of NLGP.

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  1. Dr R Baral, Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mookherjee Road, Kolkata 700026, India. E-mail: baralrathin@hotmail.com

Authors and Affiliations

  1. Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata, India

    Krishnendu Chakraborty, Anamika Bose, Tathagata Chakraborty, Koustav Sarkar, Shyamal Goswami & Rathindranath Baral

  2. Unit of Clinical Biochemistry, Chittaranjan National Cancer Institute, Kolkata, India

    Smarajit Pal

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  1. Krishnendu Chakraborty
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Chakraborty, K., Bose, A., Chakraborty, T. et al. Restoration of dysregulated CC chemokine signaling for monocyte/macrophage chemotaxis in head and neck squamous cell carcinoma patients by neem leaf glycoprotein maximizes tumor cell cytotoxicity. Cell Mol Immunol 7, 396–408 (2010). https://doi.org/10.1038/cmi.2010.29

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