Evidence map›Paper›PMID 42608132›Full record

ArticleJournal for immunotherapy of cancer2026

Dihydropyrimidine dehydrogenase modulates immune response to checkpoint inhibition in mismatch repair deficient/microsatellite instability-high colorectal cancer.

Shivani Soni, Francesca Battaglin, Sofi Castanon, Yan Yang, Goar Smbatyan, Lesly Torres Gonzalez, Jae Ho Lo, Pooja Mittal, Edgar Gonzalez, Aaron G Baugh and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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.

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

26 authors.

Shivani SoniDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Francesca BattaglinDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.ORCID http://orcid.org/0000-0002-9869-0163
Sofi CastanonDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Yan YangDepartment of Population and Public Health Sciences, USC Keck School of Medicine, Los Angeles, California, USA.
Goar SmbatyanDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Lesly Torres GonzalezDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Jae Ho LoDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Pooja MittalDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Edgar GonzalezDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Aaron G BaughDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.ORCID http://orcid.org/0000-0001-8763-509X
Steve Soto TrujilloDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.ORCID http://orcid.org/0009-0001-5709-8542
Karam AshouriDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.ORCID http://orcid.org/0009-0000-1825-1033
Sandra AlgazeDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.ORCID http://orcid.org/0000-0001-7233-5019
Priya JayachandranDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Wu ZhangDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Indrakant K SinghDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Krisida CermaMedical Oncology, Veneto Oncology Institute, Padua, Veneto, Italy.
Francesca BergamoMedical Oncology, Veneto Oncology Institute, Padua, Veneto, Italy.
Sara LonardiMedical Oncology, Veneto Oncology Institute, Padua, Veneto, Italy.ORCID http://orcid.org/0000-0002-7593-8138
Yong ZhangDepartment of Pharmacology and Pharmaceutical Sciences, USC Alfred E Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, California, USA.
Steve A KayDepartment of Neurology, USC Keck School of Medicine, Los Angeles, California, USA.
Jian YuDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Lin ZhangDivision of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Joshua MillsteinDepartment of Population and Public Health Sciences, USC Keck School of Medicine, Los Angeles, California, USA.
Evanthia T Roussos Torres *Division of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Heinz-Josef Lenz *Division of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, California, USA lenz@usc.edu.

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

backgroundTreatment with immune checkpoint inhibitors (ICIs) has radically improved outcomes for patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). Intrinsic and acquired resistance, however, remains an important concern. Pyrimidine pathway regulates the innate immune response and may offer an opportunity to enhance ICI efficacy via modulation of pyrimidine metabolism. Identification of primary, adaptive and acquired resistance mechanisms and development of actionable strategies to overcome resistance and expand the benefit of ICI is paramount. Our group is the first to show that the dihydropyrimidine dehydrogenase (DPD; gene

methodsRetrospective analysis of germline single nucleotide polymorphisms was done in patients with MSI-H CRC cohort (Veneto Institute of Oncology; OIOV-IRCCS, Padua, Italy) treated with immunotherapy.

resultsIn our real-world data analysis, genetic variants in

conclusionOur results showed that the pyrimidine pathway has a strong association with immunotherapy treatment response in CRC. These findings may support the development of novel treatment strategies exploiting DPD inhibition in MSI-H tumors and their quick integration into clinic.

Indexed as

Colorectal NeoplasmsDihydrouracil Dehydrogenase (NADP)DNA Mismatch RepairImmune Checkpoint InhibitorsMicrosatellite InstabilityAnimalsFemaleHumansMaleMiceRetrospective StudiesDihydrouracil Dehydrogenase (NADP)Immune Checkpoint InhibitorsColorectal CancerGastrointestinal CancerImmune Checkpoint InhibitorImmune modulatory

Identifiers

PMID42608132
PMCPMC13504844

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