Immunotherapy with guts - a review of microbial therapeutic adjuncts for immunotherapy in solid tumors

Sep 23, 2026

Uploaded by Putri

Immunotherapy has changed management of some solid tumors, yet its benefit remains restricted to patients with “hot” or immunogenic tumors. This review evaluates how gut microbiome modulation may act as a co-therapy for immune checkpoint inhibitors, aiming to convert “cold,” immune-unresponsive tumors into “hot” states through probiotic-, consortium-, and fecal microbiota transplant-based approaches. Current evidence suggests potential clinical benefits alongside manageable safety considerations.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Background

Methods

Results

Conclusion

Implications for Practice

Introduction

The Oncologist, 2026, 31, oyag131 [https://doi.org/10.1093/oncolo/oyag131](https://doi.org/10.1093/oncolo/oyag131) [Published: 9 April 2026](Published: 9 April 2026) Review Article Immunotherapy with guts: a review of microbial therapeutic adjuncts for immunotherapy in solid tumors Kelly Pum1, , Emil Lou2,3, , Paolo Goffredo3,4, , Cyrus Jahansouz3,4, , Subbaya Subramanian2,3,4,5, , Ajay Prakash2,3,*, 1College of Biological Sciences, University of Minnesota, Minneapolis, MN, 55108, United States 2 Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School, Minneapolis, MN, 55455, United States 3 Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN, 55455, United States 4 Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, 55455, United States 5Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, 55455, United States *Corresponding author: Ajay Prakash, MD, PhD, Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, 516 Delaware St SE, Minneapolis, MN 55455, USA ([praka086@umn.edu](praka086@umn.edu)) . Abstract Background: Immunotherapy has transformed the management of some solid tumor types, but its impact has been limited to the subset of cancer patients who have “hot” or immunogenic tumors. Num2erous studies are based on strategies for turning “cold,” or immune-unresponsive, tumors into a “hot” state. The gut microbiome has emerged as a potential co-therapy for standard immune checkpoint inhibitors (ICIs) to achieve this goal. Recent approaches have primarily focused on the use of probiotics, microbial consortia, or fecal microbiota transplantations in combination with anti-PD-1 and anti-CTLA-4 antibodies. Methods: This review highlights the current status of microbiome modulation and its potential impact on clinical practice. Probiotics, such as CMB588, and microbial consortia have been selected following successful preclinical studies. These taxa may initiate T cell infiltration and are commonly found in the microbial profiles of individuals who have previously responded to immunotherapy. Results: Several trials with these therapies have had success and noted minimal safety concerns compared to monotherapy treatments. Fecal microbiota transplantation (FMT), originally used to treat Clostridium difficile infections, has also demonstrated promising results in increasing immune checkpoint inhibitor (ICI) efficacy across various cancer types and is being utilized in multiple ongoing trials. Conclusion: These therapeutics form the foundation for exciting possibilities in immunotherapy and improving patient outcomes. Key words: immunotherapy; clinical trials; tumor microenvironment; solid tumors; immune checkpoint inhibitors; microbial modulation Implications for Practice Expanding immunotherapy to larger patient populations remains a critical goal of cancer management. Modulating the microbiome, with the addition of specific taxa or a complete microbial environment, may serve as a powerful immunotherapeutic adjunct. The microbial consortia MET4, along with several FMT studies, have demonstrated promising preliminary outcomes which may be incorporated into clinical practice soon. However, ongoing trials face challenges in funding, regulatory support and patient enrollment, resulting in slow development of these products and gaps in the clinical data. Advancing patient care will require further clinical support for translational research and advocacy for lowered trial development barriers. Received: August 26, 2025. Accepted: March 31, 2026 © The Author(s) 2026. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)), which permits noncommer

FAQs

How does the gut microbiome relate to improving solid-tumor immunotherapy?

The gut microbiome is proposed as a co-therapy to complement immune checkpoint inhibitors and help shift “cold” tumors toward a more immunogenic “hot” state through microbiome modulation.

What microbiome-based strategies are discussed in the review?

The review focuses on probiotics, microbial consortia, and fecal microbiota transplantation, including approaches combined with anti-PD-1 and anti-CTLA-4 antibodies.

What evidence is reported regarding clinical impact and safety?

Trials using these microbiome-modulating therapies have reported success and noted minimal safety concerns compared with monotherapy, and FMT has shown promising results for increasing ICI efficacy across cancer types.

Sep 23, 2026

Uploaded by Putri