The substances produced by some types of "good" microorganisms present in the intestine (microbiota) seem able to enhance the activity of cytotoxic lymphocytes and to improve the effect of oncological immunotherapy.
Since the first years of experimentation of tumour immunotherapy (i.e. the therapy which seeks to enhance the activity of the immune system to eradicate cancer) we have tried to understand whether the intestinal microbiota (the set of "good" microorganisms of the intestine) could have a positive role in all this, given that a series of molecules capable of stimulating our defensive system are born right in the intestine.
The microbiota, however, is composed of an enormous number of bacterial cells, varying from individual to individual (according to some estimates, 100 trillion), and it is not easy for researchers to disentangle themselves in this world.
Now a study conducted by the Universities of Würzburg and Marburg (Germany), and published in the scientific journal Nature Communications, enables us to clarify some important aspects of the relationship between immunity and bacteria, thus marking the way for new, possible therapeutic applications.
In particular, the study shows that some substances (short-chain fatty acids) produced by certain intestinal bacterial species profoundly influence the action of cytotoxic lymphocytes and other cells of the immune system that are highly effective in the fight against cancer. For this reason, by intervening in the same bacteria, or by administering short-chain fatty acids, it seems possible, at least in theory, to enhance the antitumour response.
Eyes on CD8 lymphocytes
To test this hypothesis, the researchers conducted a series of laboratory experiments and demonstrated that short-chain fatty acids, especially butyric and pentanoic acids, increase the "expression" of lymphocytes called CD8 cytotoxic T.
This is probably because these acids are used as "biological fuel" by the lymphocytes themselves.
Short-chain fatty acids also curb certain substances which, on the contrary, act as silencers of the immune system. All this results in an increase in the overall immune response against cancer cells.
In subsequent tests, the German researchers then showed that the administration of pentanoic acid to laboratory animals with pancreatic tumours and melanoma (the most dangerous skin cancer) also results in an enhancement of immunotherapy based on CAR-T cells (Chimeric Antigen Receptor T cells), already successfully used against some forms of solid and haematological cancer.
The CAR-T cells, let us remember, are T lymphocytes extracted from the patient, modified in the laboratory through genetic engineering techniques and then fed back into the patient's blood.
Practical applications
Thanks to the results obtained, it is thought that an action on the microbiota (e.g. with a boost to the proliferation of the species Megasphaera massiliensis, a strong producer of pentanoic acid), or an administration of specific short-chain fatty acids, could give the CAR-T a new potency, especially against some types of leukaemia, which so far have not been very sensitive to this type of treatment.
Finally, apart from the individual applications, the study confirms that the microbiota is of crucial importance, and that – on knowing it better - it will probably be possible to exploit its characteristics more effectively.
