Fig. 2
From: Activities of stromal and immune cells in HPV-related cancers
Stromal cells support HPV-related carcinogenesis through paracrine stimulation. Stromal cell plays a central role in HPV-related carcinogenesis. Cytokines and chemokines secreted by keratinocytes and HPV-infected cells (IL-1β, IL-6, IL-8, TGF-β, CXCL12 and bFGF) induce normal fibroblasts to become CAFs, which secrete a number of proinflammatory factors, chemoattractant and extracellular matrix remodelling molecules. This remodelling causes alteration of cancer cell polarity, migration, cell-cell communication and cell growth. The activation and attraction of immune inflammatory and modulatory cells, including M2 macrophages (TAM), neutrophils (TAN), mast and myeloid-derived suppressor cells (MDSCs) by key chemokines, further support the creation of a poor prognosis condition where T lymphocytes and NK cytotoxic responses are impaired, in contrast to the increased activity of Treg [5, 26, 27, 42, 43, 134]