**3. Deregulation of TLR expression may promote cancer initiation and development**

The expression of TLRs, their function in cancer cells and the association with tumor progression have become a very exciting field of investigation. However, it is well reported that functionally active TLRs are expressed by multiple immune cells such as human cancer cells (lung, gastric, laryngeal, cervical, prostate, etc.) [2, 27]. The general pattern of TLR expression in tumor cells suggests that TLR-mediated signaling plays a crucial role in cancer tumor development. It is possible that tumor cells express multiple TLRs to recognize various danger-associated molecular patterns (DAMPs) in their microenvironment. This may enhance the biological process mediated by TLR activation to produce favorable conditions for growth and survival. However, the significance of the expression of several TLRs in various cancer cells is not fully understood. Semlali et al. reported that different TLRs, specifically TLR 2, 6, and 9, are expressed in normal colon epithelial tissues, and their expression has been reported to be decreased in most colorectal cancer tissues compared to normal matching tissues [8]. Conversely, TLR4 expression increases in colon and breast cancer tissues compared to normal tissues [28, 29]. To date, TLRs have been found to have the opposite effect on tumor progression. On the one hand, TLR ligands can suppress tumor growth. On the other hand, TLR agonists can promote the survival of malignant cells and increase their resistance to chemotherapy [30]. It is possible that tumor cells express multiple TLRs to recognize various DAMPs in their microenvironment. This may enhance the biological process mediated by TLR activation to produce favorable conditions for growth and survival. Furthermore, the ligation of TLRs in tumor cells increases the production of immunosuppressive cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-β [2], suggesting that tumor cells also utilize TLR activation to escape from tumor immune surveillance. However, several available studies support the idea that TLRs are cancer inhibitors. *Thus, further investigation is mandatory to decipher the role and the genetic variation of TLRs in cancer.*
