**1. Introduction to the toll-like receptors (TLRs)**

TLRs are trans-membrane proteins receptors that trigger the signal transduction cascades upon binding with specific pathogen-associated molecular patterns (PAMPs) ligands, and earlier have been thought to be restricted to immune cells. TLRs play a key role in the innate immune system as well as subsequent induction of adaptive immune responses against microbial infection or tissue injury [1]. TLRs receptors triggers immune response against various invading pathogens by recognizing receptor specific to PAMPs, which is highly conserved and derived from potential pathogenic microorganism such as bacteria, viruses, fungi and parasites [2, 3]. The very well-known one such PAMPs is lipopolysaccharides (LPS) acts as ligands for TLRs, which is found on outer cell wall of gram negative bacteria [4]. Moreover, TLR receptors also recognize endogenous damage-associated molecular patterns (DAMPs), derived from injured host cells including necrotic cancer cells, dead or dying cells, or products released from cells in response to signals such as hypoxia and epithelial cells [5]. These PAMPs and DAMPs together help

in discriminating both self and non-self-danger signals [1, 2]. Specific TLR receptors recognizes distinct microbial ligands i.e. lipopeptides, lipoteichoic acids, LPS, peptidoglycans, flagellins, viral and bacterial nucleic acids etc. [6]. These ligands binds to specific TLR receptors, initiate cascade pathway which plays important role in maintenance of cellular homeostasis, cell proliferation or apoptosis, cell differentiation, as well as induction of inflammatory cytokines like interferons (IFNs), interleukins (IL2, IL6, IL8, IL12, IL16), and TNF-α to get rid of pathogens [3, 7].

Cancer develops when uncontrolled growth of abnormal cells occurs anywhere in a body and further metastasized to distant part of the body. In order to deepen our understanding of cancer biology, it is very important to address the factors that are involved in the tissue repair process, such as cytokines, chemokines, growth factors and TLR signaling, which are the key determinants of cancer progression [8, 9]. TLR signaling is known to activate nuclear factor-κB (NFκB) and mitogen-activated protein kinase (MAPK) pathways [10]. NF-κB in turn, regulates the expression of anti-apoptotic genes, and activation of the complement pathway depending upon type of ligands it sensed [11, 12]. Furthermore, TLRs are expressed not only on the surface of immune cells but also on cancerous cells [13]. In humans, TLRs (TLR1-TLR10) play very important role in diseases progression and the TLRs signaling have been well studied in various diseases including cancer [14]. The TLRs and their intracellular signaling components play very important role in the onset of inflammatory diseases [4]. Recent studies have revealed that chronic inflammation can increases the risk of cancer development and also promote its progression [14]. TLRs signaling also plays a crucial role in the development of chemo-resistance; *Michael et al., (2006)* shows TLR4/MYD88 signaling promotes tumor growth and contributes to chemo-resistance against paclitaxel in ovarian cancer [9]. Moreover, a recent study delineates that high TLR7 and TLR8 expression promotes chemo-resistance, leading to increases increased tumor cell proliferation in human pancreatic cancer [15]. However, the role of TLR signaling is still not completely understood in cancer progression; some studies suggest it has both pro-tumor as well as anti-tumor effects. To date, TLRs are documented to play supportive role for initiation, progression and metastatic potential of cancer [16, 17]. One the other hand, they are capable of maintaining antitumor environment by eliciting activation of anti-tumor mediators such as type I interferon [18]. This book chapter highlights the current understanding of role of TLRs and addresses a crucial link between carcinogenesis and immune cells, TLRs signaling and antagonist.
