Page 194 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 10
tumour necrosis factor (TNF)-α and interleukin (IL)-12. This cytokine milieu triggers a Th1 cell mediated immune response with generation of cytotoxic effectors cells. These processes are depicted in figure 1.
Figure 1. TLRs and T helper cell responses.
PAMPs from invading pathogens bind with TLRs expressed in DCs, and DCs become activated and mature to active naive T cells. Naive T cells are primed toward specific T helper profiles: Th1, Th2, which can produce cytokines and in turn establish resistance to external pathogen invasion. [49]
In recent years, it has been uncovered that TLRs are also involved in the development of a variety of malignancies.[48, 49] Numerous studies have shown an abnormal expression of TLRs in tumor cells as compared to normal tissue, including in cervical cancer. Through mechanisms not fully understood, TLRs can induce a dysfunctional inflammatory response in a carcinogenic environment. TLR2/3/4/5/9 have been most frequently described in tumor tissues. This dysfunctional inflammatory response contributes to carcinogenesis through several mechanisms: an anti-apoptotic effect through activation of NF-kB, induction of oxidative damage to DNA, activation of the tissue repair response and promotion of angiogenesis through recognition of
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