Altering the gut microbiome and tumor microenvironment in advanced liver cancer: A phase II study of nivolumab, tadalafil and oral vancomycin in patients with refractory primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal or pancreatic cancers
- PMID: 40789510
- DOI: 10.1016/j.canlet.2025.217975
Altering the gut microbiome and tumor microenvironment in advanced liver cancer: A phase II study of nivolumab, tadalafil and oral vancomycin in patients with refractory primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal or pancreatic cancers
Abstract
A phase II study was conducted in patients with primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal (CRC) or pancreatic (PDAC) cancers to assess the effect of nivolumab (anti-PD1), oral vancomycin and tadalafil. Patients were treated with 480 mg nivolumab intravenously every 4 weeks, oral 10 mg tadalafil daily and 125 mg vancomycin orally every 6 h days 1-21 of a 28-day cycle. The primary endpoint was best overall response. Secondary endpoints included analysis of the gut microbiota, serum bile acids and immune cells in peripheral blood. A total of 22 patients were enrolled (6 HCC, 7 CRC and 9 PDAC patients). Three out of 16 evaluable patients (2 patients with HCC and 1 patient with CRC) demonstrated stable disease as best response. No unexpected adverse events were observed. A decrease in secondary bile acids along with changes in gut microbiota were observed. Vancomycin/Tadalafil/Nivolumab treatment did not cause any apparent change of major immune cell frequencies in peripheral blood however, a significant change was observed in monocyte subsets. Treatment was well tolerated and led to changes in the gut microbiome along with changes in the bile acid pool and myeloid cells in peripheral blood. No clinical activity was observed.
Keywords: Bile acid metabolism; Gut microbiome; Hepatocellular carcinoma; Immunomodulation; Liver metastases; Myeloid-derived suppressor cells; Natural killer T cells; Regulatory T cells; Tumor microenvironment; Tumor-associated macrophages.
Published by Elsevier B.V.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), NCI (ZIA BC 011345). The contributions of the NIH author(s) were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services. The authors declare that they have no known financial or personal conflicts of interest that could have influenced the work reported in this manuscript. No funding, grants, or financial support was received from any organization that could be perceived as a potential conflict of interest If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
