Cancer research is increasingly shifting its focus from targeting tumors alone to the entire biological ecosystem of the host. A emblematic example of this paradigm shift is the TACITO study, a phase 2 randomized trial coordinated by the Fondazione Policlinico Universitario Agostino Gemelli IRCCS and the Università Cattolica, which analyzed the impact of fecal microbiota transplantation (FMT) in patients with metastatic renal cell carcinoma treated with the combination of pembrolizumab (immunotherapy) and axitinib (an anti-VEGF receptor targeted therapy), the standard first-line treatment.
The underlying hypothesis, as explained by Gianluca Ianiro, the study’s principal investigator, is that the gut microbiota serves as an essential mediator of immunotherapy efficacy. «The working hypothesis was that transplanting an “adequate” intestinal microbiota could improve the response to immunotherapy», Ianiro said, stressing that this is the first trial in the world to compare donor responder FMT against placebo in this specific clinical setting.
Clinical Data: A Qualitative Leap in Survival
The results published in Nature Medicine show a clear difference between the patients who received the transplant and the control group. Although the primary endpoint (the percentage of patients progression-free at 12 months) displayed a positive trend (about 70% vs 41%) without fully achieving statistical significance, the secondary endpoints were described by the investigators as “extremely promising”.
In particular, Professor Roberto Iacovelli, co-PI of the study, associate professor of Oncology at the Università Cattolica del Sacro Cuore and head of Medical Oncology at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, noted that «the median progression-free survival (PFS) was markedly higher in the group that received FMT: 24 months vs 9 months in the control group, with a 50% reduction in the risk of progression». The objective response rate also rose significantly, increasing from 32% among controls to 52% among the transplanted patients.
The Integrated Medicine Perspective
From the viewpoint of integrative medicine, the study adds a crucial piece: the microbiota is not merely a passive “tenant,” but a dynamic element capable of modulating inflammation and angiogenesis, two critical factors in renal cell carcinoma. The genomic analysis conducted by Professor Nicola Segata, a genetics professor at the University of Trento, confirmed that the clinical benefit is tied not only to the engraftment of donor strains and greater microbial diversity but also to the loss of certain bacterial strains deemed harmful.
Looking Toward the Future
The implications for the future run deep. As suggested by Professor Antonio Gasbarrini, scientific director of Gemelli, the microbiota could eventually be used as a predictive biomarker: «A better understanding of the “adequate” microbiota could allow us to modulate its composition to optimize responses to immunotherapy, and not necessarily through FMT». This opens the door to precision interventions, through bacterial cocktails or targeted microbial consortia (live biotherapeutic products).
The TACITO study ultimately demonstrates that enhancing the immune response cannot occur without the health of the intestinal environment. For clinicians, this means considering microbiota modulation as a necessary complementary strategy to optimize the outcomes of standard therapies, turning a biological stimulus into a tangible therapeutic advantage for the patient.
Study
Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial; Serena Porcari, Chiara Ciccarese, Vitor Heidrich, Debora Rondinella, Gianluca Quaranta, Andrea Severino, Daniela Arduini, Sebastiano Buti, Giuseppe Fornarini, Francesca Primi, Luciano Stumbo, Diana Giannarelli, Giulia Claire Giudice, Alessandra Damassi, Julio Rodrigo Giron Berríos, Michal Punčochář, Thomas B. Barbazuk, Gianmarco Piccinno, Federica Pinto, Federica Armanini, Francesco Asnicar, Giovanni Schinzari, Lisa Derosa, Guido Kroemer, Gianluca Ianiro; Nature Medicine (2026)
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