Kidney cancer, microbiota transplantation improves response to immunotherapy
In Nature Medicine the study coordinated by scientists from the Catholic University and Policlinico Gemelli Irccs in Rome. Principal investigatorGianluca Ianiro: a key modulator of drug response
Transplantation of intestinal bacteria from a donor may potentially help cancer treatment by enhancing the effects of immunotherapy. These are the conclusions of a clinical study carried out in Italy and published in the journal Nature Medicine. Coordinated by scientists from the Università Cattolica del Sacro Cuore and the Fondazione Policlinico Universitario Agostino Gemelli Irccs, the TACITO study, a multicentre phase 2 clinical trial, evaluated whether transplanting microbiota from donors (specifically from cancer patients who had achieved a complete response to immunotherapy) could improve clinical outcomes in patients with advanced, metastatic renal cancer.
The Studio
The patients involved, 45 in all, were treated with the standard combination of an immunotherapy (pembrolizumab) and axitinib (a targeted anti-angiogenic therapy, i.e. against the formation of blood vessels that help the tumour to grow). The patients were divided into two groups, the first receiving the microbiota transplant, the others a placebo treatment. Well, it turned out that the transplantation of good gut bacteria halved the risk of disease progression in patients, i.e. patients who received the transplant survived an average of 24 months free of disease progression, compared to 9 months in the placebo group. Notably, the benefits of microbiota transplantation combined with immunotherapy were particularly evident in patients who generally have fewer treatment options and worse outcomes. It is important to note that the clinical benefit is more associated with the elimination of specific 'harmful' bacterial strains than with the overall levels of engraftment of the microbiota transplant.
The results
"These results provide further evidence that the gut microbiota is a key modulator of the response to immunotherapy," points out principal investigator Gianluca Ianiro. 'Transplantation of microbiota from carefully selected donors could become an important complementary strategy to improve outcomes in metastatic renal carcinoma, probably by providing an immunological stimulus that enhances the response to treatment'. For more than a decade, immunotherapy - drugs that can 'reactivate' and trigger the immune system against the tumour - has been revolutionising the treatment of many cancer diseases. "Immunotherapy has long been the standard of treatment for kidney tumours, together with anti-angiogenic targeting drugs," recalls Professor Giampaolo Tortora, Professor of Medical Oncology at the University and Director of the Comprehensive cancer centre of the Agostino Gemelli Irccs University Polyclinic Foundation. "Unfortunately, some patients do not respond immediately to treatment, while others respond modestly. Researchers around the world are therefore trying to understand how to enhance the response to these drugs'.
The Outlook
All this opens up a very encouraging scenario ahead. 'In the future, the patient's microbiota may be studied as a predictive biomarker of response to cancer immunotherapy,' concludes Professor Antonio Gasbarrini, Scientific Director of the Fondazione Policlinico Universitario Agostino Gemelli Irccs and Professor of Internal Medicine at the Università Cattolica del Sacro Cuore. A better knowledge of the 'adequate' microbiota may allow us to modulate its composition with a view to responding to immunotherapy and not necessarily through FMT. New administration techniques are being studied (e.g. lyophilised capsules, forerunners of bacterial cocktails, i.e. microbial consortia or live biotherapeutic products)'.
