HPV16‐associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells. Issue 4 (26th June 2014)

• Record Type: Journal Article
• Authors: Stone, Simone Cardozo; Rossetti, Renata Ariza Marques; Bolpetti, Aline; Boccardo, Enrique; de Araujo Souza, Patricia Savio; Lepique, Ana Paula
• Is Part Of: Journal of leukocyte biology. Volume 96:Issue 4(2014)
• Page Start: 619
• Page End: 631
• Publication Date: 2014-06-26
• Subjects: human papillomavirus -- cytokines -- systemic effects -- immune evasion -- cell signaling; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0513-282R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : HPV16 associated tumors induce cell proliferation, modulate cell signaling, and cytokine expression in antigen presenting cells, favoring regulatory T cell expansion in peripheral lymphoid organs. Abstract : Tumors are complex structures containing different types of cells and molecules. The importance of the tumor microenvironment in tumor progression, growth, and maintenance is well‐established. However, tumor effects are not restricted to the tumor microenvironment. Molecules secreted by, as well as cells that migrate from tumors, may circulate and reach other tissues. This may cause a series of systemic effects, including modulation of immune responses, and in some cases, leukocytosis and metastasis promotion. Leukocytosis has been described as a poor prognostic factor in patients with cervical cancer. The main etiological factor for cervical cancer development is persistent infection with high oncogenic risk HPV. Our laboratory has been exploring the effects of high oncogenic risk, HPV‐associated tumors on lymphoid organs of the host. In the present study, we observed an increase in myeloid cell proliferation and alteration in cell signaling in APCs in the spleen of tumor‐bearing mice. In parallel, we characterized the cytokines secreted in the inflammatory and tumor cell compartments in the tumor microenvironment and in the spleen of tumor‐bearing mice. We show evidence of constitutive activation of the IL‐6/STAT3 signaling pathway in the tumor, including TAMs, and in APCs in the spleen. We also observed that IL‐10 is a central molecule in the tolerance toward tumor antigens through control of NF‐κB activation, costimulatory molecule expression, and T cell proliferation. These systemic effects over myeloid cells are robust and likely an important problem to be addressed when considering strategies to improve anti‐tumor T cell responses.