Authors: Tibor Hajto.
Many years ago, a great deal of research was carried out to improve the suppressed activity of innate immune system in cancer patients using various immunomodulators originated from microorganisms or plants. However, more than 30 years ago these investigations were stopped since their repeated applications often led to a tolerance which could not be explained at the level of science at that time and in spite of a great amount of data, the curative role of innate system was poorly understood. Today, growing evidence suggests that the adaptive cytotoxic T cells have rather prophylactic effects working more proficiently in the early phases of tumor development, whereas the innate cellular system acts more curatively in parallel with disease progression. It’s now also known, that tumor-induced dysregulation of the innate immune system leads to a decreased function of type-1 effector cells and a predominance of type-2 cells, promoting the development of tumors. In this review article a number of results originating from old publications are discussed and presented again in order to interpret them according to our current knowledges which appear to be helpful for more correct application of standardized and evidence based immunomodulators (SEIM) from plant or microbes. Conclusions: 1.) Since the chemistry is not able to produce appropriate structures of Pathogen Associated Molecular Pattern (PAMP) molecules, we need PAMP containing SEIM from plants and microbes which can activate the type-1 phagocytic cells by binding their Pattern Recognition / Toll Like Receptors (RCC/TLR) on their cell membrane. 2.) PAMP molecules have a direct effect only on RCC/TLR molecules of phagocytes and only thereafter with a minimum time delay of 24 hours are the regulatory cascade mechanisms activated which can increase the function of the for the curative tumor defense important MHC-I unrestricted effectors (such as NK, γδT and type-1 NKT cells). 3.) A permanent activation of phagocytic cells can result in a decrease in MHC-1 unrestricted immune function, which may explain the tolerance observed often during continuous SEIM treatments. 4.) Since short-term activations of type-1 phagocytic cells causes more antitumor benefit, on the base of kinetic investigations a necessity to insert of 72h therapy-free intervals during SEIM therapy must be taken into consideration.
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