Evidence map›Paper›PMID 42427432›Full record

ArticleCellular and molecular bioengineering2026

Toward a Dual-Axis Model of Microbiome Modulation in Cancer Immunotherapy: Pathobiont Elimination and Functional Ecosystem Restoration.

Diwakar Davar, Hassane M Zarour, Giorgio Trinchieri

Abstract read
In one paragraph

Article in Cellular and molecular bioengineering, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Diwakar DavarDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, UNITED STATES.
Hassane M ZarourDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, UNITED STATES.
Giorgio TrinchieriLaboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD., UNITED STATES.

Funding

LICI Microbiome and Genetics CoreZICBC011237 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI OHUIGIN, COLM · 2009 to 2025
$28.3M
Role of mouse microbiome in cancer and inflammationZIABC011153 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TRINCHIERI, GIORGIO · 2009 to 2025
$22.0M
Role of inflammation, innate resistance, and immunity in carcinogenesis.ZIABC010793 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TRINCHIERI, GIORGIO · 2009 to 2025
$16.8M
Project 5: Microenvironment manipulation using anti-angiogenics to improve immunotherapy in melanomaP50CA254865 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELGOFFE, GREG M., KIRKWOOD, JOHN MUNN · 2021 to 2025
$10.4M
Regulation of human dendritic cell activationZIABC011152 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TRINCHIERI, GIORGIO · 2009 to 2025
$8.6M
Neoadjuvant Immunotherapy with Intratumoral CPG and PD-1 Blockade in MelanomaR01CA257265 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVAR, DIWAKAR, ZAROUR, HASSANE M · 2021 to 2025
$2.6M
Fecal Microbiota Transplant and PD-1 blockade in MelanomaR01CA222203 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZAROUR, HASSANE M · 2018 to 2022
$2.5M
Therapy with fecal microbiota transplantation and immune checkpoint blockade for solid tumorsU01CA268806 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HASSANE M ZAROUR · 2022 to 2026
$2.4M
Intramural NIH HHS ZIA BC010793Intramural NIH HHS ZIA BC011152Intramural NIH HHS ZIA BC011153Intramural NIH HHS ZIC BC011237NCI NIH HHS P50 CA254865NCI NIH HHS R01 CA222203NCI NIH HHS R01 CA257265NCI NIH HHS U01 CA268806
6 · The paper itself

Abstract

Purpose: The gut microbiome is increasingly recognized as a modulator of cancer immunotherapy efficacy, including responses to immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy. Recent clinical trials of microbiome-targeted interventions such as fecal microbiome transplantation (FMT) and live biotherapeutic products (LBPs) suggest the potential to enhance antitumor immunity and improve clinical outcomes. Yet responses remain heterogeneous and are not fully explained by engraftment of donor taxa alone. Methods: We integrate evidence from interventional trials, observational cohort studies, and principles from gut microbial ecology to develop a model hypothesis on how microbiome-targeted therapies may shape response to immunotherapy, with potential to inform future trial design, analyses, and interpretation. Results: Drawing on the available evidence, we propose that therapeutic perturbation of the gut microbiome may augment immunotherapy efficacy through two parallel axes: (1) elimination of immunosuppressive pathobionts that restrain CD8+ T-cell activation and promote myeloid-mediated immunosuppression, and (2) functional restoration of the gut ecosystem through engraftment of taxa that provide metabolites, structural cues, and immunoregulatory signals required for effective antitumor immunity. The success of both axes appears to depend on ecological processes governed by predator-prey dynamics, including colonization resistance, resilience of the resident microbiota, and the ability of administered organisms to displace entrenched dysbiotic communities. This ecological lens may help to explain discrepancies across trial designs, donor types, and intervention modalities, and suggests that complete donor engraftment is neither necessary nor sufficient for clinical benefit. Conclusions: A dual-mechanism model of pathobiont elimination and functional microbial restoration may help explain microbiome-mediated enhancement of cancer immunotherapy, highlighting a balanced immune permissive gut ecosystem as a key determinant of therapeutic success.

Indexed as

colonization resistanceCTLA-4cutaneous melanomacytotoxic T-lymphocyte associated protein 4fecal microbiome transplantationFMTgut ecologygut microbiomeICIimmune checkpoint inhibitorLBPlive biotherapeutic productsnon-small cell lung cancerNSCLCPD-1predator-prey dynamicsprogrammed death 1RCCrenal cell carcinoma

Identifiers

PMID42427432
PMCPMC13348773

What Socratic holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.