Neutrophil granulocytes are a group of white blood cells that can be used in the treatment of tumors following subjection to a special training programme. In other to make the training of this cells possible a long-chain sugar molecule (beta-glucan) which occurs as a natural fibre mainly in the cell walls of fungi, oats or barley is used. The immune training of these cells was effective at the level of blood formation in the bone marrow and in the precursor cells of the neutrophil granulocytes. In line with this recently described mechanism, the development of new cancer immunotherapies which are capable of enhancing treatment of cancer patients will be considered and developed in the future.
The protective effect of the immune cells gets nullified by tumor cells upon evasion of the immune system. This because there are a number of ways by which tumor cells can evade immune cells. The primary objective of immunotherapies is the prevention of immune cell evasion by tumor cells and possible redirection of the natural defense mechanisms against the cancer cells.
T cells, dendritic cells and certain antibodies are the major focus of modern immunotherapies. This is because they are specialized immune defense systems. These specialized immune system are capable of recognizing, suitable structures on tumor or immune cells and initiate a precisely tailored defense reaction. Following this, it was possible to show that the non-specific immune response example Neutrophil granulocytes which are part of the innate immune system can be weaponized against tumors through special training and education. Based on this mechanism, novel cancer immunotherapies are conceivable which are capable of improving the chances for treatment for certain patients in the future.
Neutrophil granulocytes which are the most common sub-group of the white blood cells and members of the innate non-specific immune defence system are at the heart of this newly described mechanism. As opposed to the adaptive immune system which first analyzes antigens in thoroughly, and in time activates specialized immune cells targeted at the foreign bodies (antigens) – the innate, non-specific system acts as rapidly with force in response to pathogens that invade the body or attempt to degenerate cells. The reaction is swift and stereotyped.
It is possible to train the non-specific immune response by stimulation. This training enables certain factors of the rapid response force to exhibit altered properties and perform their tasks better and over a longer period of time than before: in this way the intensity of impact increases. The novel approach is the use of this method in therapies targeted against tumors.
Neutrophil granulocytes play an essential part in this process. They do this by accumulating in the micro-environment of the tumor or migrate into it. These tumor-associated neutrophils found directly in the tumor are capable of inhibiting tumor growth. However some have tumor-promoting features. One assumption is that the tumor produces substances that turn the neutrophils into promoters of tumor growth. It was possible to reverse this process experimentally by training the neutrophil granulocytes as this was detrimental to the healing process. Beta-glucan was an efficient stimulant of the immune system. Administration of beta-glucan caused the proliferation of neutrophils and this resulted in decrease of tumor growth.
More importantly is the proof that neutrophil granulocytes reprogramming already starts in the bone marrow. Starting with pluripotent stem cells, a number of precursor cells develop and through haematopoiesis a number of blood cells are born. Beta-glucan is able to alter the gene activity of myeloid precursor cells from which the neutrophil granulocytes eventually develop. Eventually activities of the neutrophil granulocytes which prevent the growth of tumor are changed. This happens because the precursor cells form neutrophils that perform tumor-inhibiting functions over a longer period of time.
A profitable measure in tumor immunotherapies for the future will be the training of neutrophils in addition to existing cancer immunotherapies. This will foster knowledge of the types of tumors where this approach is efficient.