ArticleJournal for immunotherapy of cancer2026
Screening of known gut microbiome-derived metabolites in anti-tumor immunity of colorectal cancer.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost colorectal cancers (CRCs) patients with microsatellite stability (MSS) have minimal benefit from immune checkpoint inhibitor monotherapy, and even after PD-1/PD-L1 blockade, T cell function remains inadequately restored, highlighting the importance of PD-1 downstream signaling events. SHP-2 is a critical effector of PD-1 downstream signaling and plays a key role in establishing the immunosuppressive tumor microenvironment in CRC. Gut microbial metabolites are emerging as regulators of anti-tumor immunity, but their role in modulating the PD-1/SHP-2 interaction remains unknown.
methodsWe established a split-luciferase complementation screening system based on the PD-1/SHP-2 interaction and systematically screened a library of human gut microbial metabolites (n=480). The effect of candidate metabolites on T cell function was assessed
resultsWe identified the conjugated bile acids TCA and GDCA as enhancers of the PD-1/SHP-2 interaction. Mechanistically, TCA and GDCA stabilized the PD-1/SHP-2 complex through an allosteric mechanism by promoting PD-1 phosphorylation. Functionally, two metabolites suppressed CD8
conclusionsThis study reveals a "Bile acid-associated metabolites-Immune checkpoint" regulatory axis that drives immunosuppression in CRC. The identification of TCA and GDCA as endogenous enhancers of PD-1 signaling provides a mechanistic rationale for targeting these metabolites to overcome immunotherapy resistance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.