Editorial: Pattern Recognition Receptors and Cancer

The problem of cancer remains one of the most immense challenges to current biomedical research. Affecting populations in all countries and all regions, this disease is responsible formillions of deaths annually (1). Evasion of the immune system is an ominous feature of cancers, which often leads to tumor outgrowth, epithelial–mesenchymal transition (EMT), and consequently, metastatic disease. The need to understand basic mechanisms governing immune response to tumors is increasingly acute, since contemporary cancer research gradually progresses toward highly specialized personalized medicine. In this respect, oncoimmunology of pattern recognition receptors (PRRs) is a promising area of research which requires more attention and broader interpretation. The group of PRRs includes families of toll-like receptors (TLRs), NOD-like receptors (NLRs), C-type lectin receptors (CLRs), RIG-I-like receptors (RLRs), and AIM-2-like receptors (ALRs). United by two general features, these receptors are the key players in human immunity. First, they directly recognize antigen determinants of nearly all classes of pathogens [pathogen-associated molecular patterns (PAMPs)] and promote their elimination by triggering innate and adaptive immune response. Second, they recognize endogenous ligands released during cell stress [damageassociatedmolecular patterns (DAMPs)], and therefore can activate immune response in the absence of an infectious agent. In addition, PRRs are known to possess a number of other vital functions, regulating the processes of apoptosis, DNA repair, autophagy, and angiogenesis. Remarkable functional significance and diversity of biological functions are the reasons why PRRs today are an actively growing area of research. During the last decade, much research has been done to investigate the role of PRRs in tumor immunity. Accumulating evidence demonstrate that anti-tumor immunity can be stimulated through the activation of PRRs (2, 3). It has been repeatedly shown that reinforced PRR activation may protect the host from infectious agents and prevent, inhibit, or block carcinogenesis whereas disrupted or deregulated functioning of PRRs may promote cancer through weakening the immune system (2, 3). At the same time, PRR activation may stimulate cancer by creating a proinflammatory microenvironment which is favorable for tumor progression and chemoresistance development (4). Furthermore, it may also result in immunosuppression caused by chronic inflammation (2), which is known to promote the development of breast carcinoma, colorectal cancer, pancreatic adenocarcinoma, and possibly several other cancer types (5, 6). In this case, on the contrary, lower PRR activity should minimize effects of chronic inflammation such as enhancement of cancer initiation and promotion/progression and, consequently, decrease probability of tumor development (4). Therefore, the situation resembles a double-edged sword, where both sides can cut unless goldenmean ismaintained. In this respect, it is clear that a subtle balance of low and high PRR activity is required for proper functioning of the immune system. This hypothesis, initially developed for PRRs (3), may also be successfully projected on PRR intracellular signaling pathways – if their elements are overexpressed/constantly activated, it may lead to consequences similar to that