Abstract
Carcinomas are malignant tumors originated from epithelial cells. Tumor stroma is formed by other cell types such as fibroblasts, endothelial cells, pericytes, adipocytes and leukocytes that can be identified both around and within the tumor. Besides, the complexity of these structures is increased by the presence of the cellular matrix, cytokines, chemokines and growth factors secreted by the different cell types present. This combination creates a unique tumor microenvironment which may modify the properties of the transformed cells. The products of the E6 and E7 genes of human papillomavirus (HPV) are pleiotropic proteins that exert different effects on the host cells. These proteins collaborate to immortalize human keratinocytes and they alter the cell cycle and the differentiation program of these cells inducing the accumulation of mitotic defects. Moreover, E6 and E7 promote several mechanisms of immune evasion. However, most of the HPV infections are transient and are cleared by the action of the cell-mediated immune response. On the other hand, women with cervical cancer exhibit tolerance to HPV antigens which has been associated to the presence of regulatory T cells (Treg) and, to a less extent, of infiltrating macrophages. Finally, several studies have shown that high-risk HPV oncoproteins induce VEGF synthesis in keratinocytes. The increase in angiogenic activity is a fundamental step in tumor progression that may be favored not only by malignant cells, but also by infiltrating macrophages and myeloid cells, as well as by local endothelial cells and pericytes. Therefore, the study of the interactions between HPV-oncogenes expressing cells and the other cellular and non-cellular elements that constitute and regulate the tumor environment may contribute to the better understanding of the pathologic processes associated to the infection by these viruses. (AU)
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