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Journal Technologies of Living Systems №3 for 2017 г.
Article in number:
The role of tumor associated macrophages in cervical cancer progression
Keywords: macrophage inflammation cancer human papillomavirus
Authors:
O.V. Kovaleva - Ph.D. (Biol.), Research Scientist, Laboratory of regulation of cellular and viral oncogenes, Institute of Carcinogenesis, Russian Cancer Research Center, Moscow E-mail: ovkovaleva@gmail.com N.A. Oleinikova - Post-graduate Student, Department of Physiology and Pathology, Faculty of Basic Medi-cine, Lomonosov Moscow State University E-mail: ale_x_05@mail.ru N.V. Danilova - Ph.D. (Med.), Assistant, Department Physiology and Pathology, Faculty of Basic Medicine, Lomonosov Moscow State University E-mail: natalyadanilova@gmail.com P.G. Malkov - Chair of pathology, Department Physiology and Pathology, Faculty of Basic Medicine, Lomo-nosov Moscow State University E-mail: malkovp@fbm.msu.ru A.N. Gratchev - Dr. Sc. (Biol.), Head of the laboratory of tumor stromal cells biology, Institute of Carcinogenesis, Russian Cancer Research Center, Moscow E-mail: alexei.gratchev@gmail.com
Abstract:
The role of stromal cells in the development of solid tumors is well established since several decades. Tumor associated macrophages (TAMs) represent one of the key components of tumor stroma. Being prototype type 2 macrophages TAMs provide tumor with growth factors, tools for immune escape as well as enzymes and extracellular matrix components needed for metastasis. Similar to other solid tumors correlation of TAMs amount with poor prognosis was demonstrated for cervical tumors. Further for this type of tumor it was demonstrated that TAM amount increases linearly from normal tissue via various neoplasia stages. TAMs define some other features of cervical tumors, for instance TAM amount correlate with angiogenesis and lympangiogenesis. It was demonstrated that TAMs directly support angiogenesis, lympangiogeneis and tumor dissemination by production of VEGF-C. Since most of cervical tumors are associated with human papilloma virus (HPV) (up to 99%, according to some publications), the inflammatory infiltrate may have certain virus-specific peculiarities. Several studies demonstrate correlation of different HPV types with different morphological features of the tumor. Squamous cell carcinoma is associated with HPV-16 in 80-85% of cases, while the remaining 15-20% are associated with HPV-18. At the same time HPV-18 is more frequently found in adenocarcinoma, according to some reports up to 50%. As well differences in TAMs phenotype in different histological types of cervical tumors were reported. For example expression of PD-L1 in TAMs was reported for 53% cases of squamous cell carcinoma and only for 12% cases of adenocarcinoma. Considering more frequent presence of HPV-16 in squamous cell carcinoma it can be hypothesized that TAM phenotype may be directly or indirectly determined by the type of HPV present in the tumor. Unfortunately to date the number of studies dedicated to this problem is limited and no clear conclusion can be made about the properties of TAMs induced by different HPV types. Since most of the cases of cervical tumors are virus-associated and several types of HPV or even their combinations can participate in the process of carcinogenesis additional studies are needed to identify the mechanism of virus-induced stromal cells programming Further knowledge accumulation in this particular field will lead to identification of new prognostic markers of the disease and allow development of new therapeutic strategies.
Pages: 4-12
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