Since malignant tumors parallel with their progression can lose their sensitivity against the MHC-I restricted T lymphocytes because of their escape in tumor antigen presenting, we need immunomodulators which are able to activate MHC-I unrestricted tumoricidal mechanisms of innate immune system. In contrast to the adaptive system, the innate immune cells have regularly a basic activity (priming) which can determine their function ability and render  possible a polarity similar to neuroendocrine system.

Namely, innate immune cells are committed in two directions. Type-1 cells involve tumoricidal cascade mechanisms which activate the MHC-I unrestricted killer cells (such as NK-cells) and Type-2 cells activate cell proliferation by production of Growth Factors (GFs), affect chronic inflammation, stimulate the angiogenesis and inhibit the type-1 system. As shown in this paper the activity of type 1 cells is down regulated parallel with the tumor progression and available information suggest a regular tumor-induced dominance of type-2 cells. Immunomodulators must improve this disturbed balance. Type-1 natural cells can be activated only via stimulation of phagocytic cells by PAMP like structures which have always a natural origin and the chemistry is not able to produce them.In the tumoricidal activity of MHC-I unrestricted killer cells the expression of NKG2D receptors and the expression of their stress related ligands (MICA/B, UBPL1-3) have pivotal regulatory role generating the kill signal.

The aim of this review paper to support hypotheses as to whether an increase in expression of KAR on MHC-I unrestricted killer cells by evidence based plant immunomodulators and parallel stimulating the expression of stress related ligands on tumor cells by GFR inhibitors or cytostatic drugs (such as Gemcitabin) can result in clinical benefits. Case reports using standardized Rice Bran Arabinoxylan Concentrate (Biobran/MGN-3) (also known as Lentin Plus 1000) in combination with GFR inhibitors or Gemcitabin show astonishing clinical responses. Unfortunately, in spite of clinical and immunological evidences this plant immunomodulator is registered only as food supplements and a further research of these hypotheses is therefore hindered.