Open AccessHPV associated tumor cells control tumor microenvironment and leukocytosis in experimental models
Author(s) -
Stone Simone Cardozo,
Rossetti Renata Ariza Marques,
Lima Aleida Maria,
Lepique Ana Paula
Publication year - 2014
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.21
Subject(s) - tumor microenvironment , cancer research , myeloid derived suppressor cell , angiogenesis , metastasis , cytokine , immunology , biology , medicine , cell culture , cancer , suppressor , tumor cells , genetics
Human papillomavirus (HPV) is the main etiological factor for cervical cancer development. HPV is also associated with other anogenital and oropharyngeal tumors. HPV associated tumors are frequent and constitute a public health problem, mainly in developing countries. Therapy against such tumors is usually excisional, causing iatrogenic morbidity. Therefore, development of strategies for new therapies is desirable. The tumor microenvironment is essential for tumor growth, where inflammation is an important component, displaying a central role in tumor progression. Inflammation may be a causal agent, suppressor of anti‐tumor T cell responses, or may have a role in angiogenesis, drug resistance, and metastasis. The aim of this work was to investigate the role of HPV transformed cells in the tumor microenvironment and tumor effects on myeloid populations in lymphoid organs in the host. We used experimental models, where we injected cervical cancer derived cell lines in immunodeficient mice, comparing HPV positive, SiHa, and HeLa cells (HPV 16 and HPV18, respectively), with HPV negative cell line, C33A. Our data shows that HPV positive cell lines were more efficient than the HPV negative cell line in leukocyte recruitment to the tumor microenvironment and increase in myeloid cell proliferation in the bone marrow and spleen. We also observed that HPV positive cells lines expressed significantly higher levels of IL‐6 and IL‐8, while C33A expressed significantly higher levels of IL‐16 and IL‐17. Finally, in spite of cytokine secretion by tumor cells, leukocytes infiltrating SiHa and HeLa tumors displayed almost negligible STAT3 and no NFκB phosphorylation. Only the inflammatory infiltrate of C33A tumors had NFκB and STAT3 activated isoforms. Our results indicate that, although from the same anatomical site, the uterine cervix, these cell lines display important differences regarding inflammation. These results are important for the design of immunotherapies against cervical cancer, and possibly against HPV associated tumors in other anatomical sites.