Evidence map›Paper›PMID 40014402›Full record

ArticleJCI insight2025

Sequential JAK inhibition enhances antitumor immunity after combined anti-PD-1 and anti-CTLA4.

Marcel Arias-Badia, PeiXi Chen, Yee May Lwin, Aahir Srinath, Aram Lyu, Zenghua Fan, Serena S Kwek, Diamond N Luong, Ali Setayesh, Mason Sakamoto and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
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

18 authors.

Marcel Arias-BadiaDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
PeiXi ChenDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Yee May LwinDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Aahir SrinathDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Aram LyuDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Zenghua FanDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Serena S KwekDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Diamond N LuongDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Ali SetayeshDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Mason SakamotoDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Matthew ClarkDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Averey LeaDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Rachel M WoltersDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Andrew GoodearlAbbVie Bioresearch Center, Worcester, Massachusetts, USA.
Fiona A HardingAbbVie Redwood City, Redwood City, California, USA.
Jacob V GormanResearch and Development, AbbVie, North Chicago, Illinois, USA.
Wendy RitaccoAbbVie Bioresearch Center, Worcester, Massachusetts, USA.
Lawrence FongDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VAISSE, CHRISTIAN · 2003 to 2019
$21.8M
Determinants of response to cancer immunotherapyR35CA253175 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lawrence Fong · 2021 to 2026
$5.8M
NCI NIH HHS R35 CA253175NIDDK NIH HHS P30 DK063720
6 · The paper itself

Abstract

While immune checkpoint inhibition (CPI) has reshaped cancer treatment, the majority of patients with cancer do not benefit from this approach, which can also cause immune-related adverse events. Induction of IFN-γ responses is thought be necessary for antitumor immunity, but growing evidence also implicates IFN-γ as a tumor-intrinsic mediator of CPI resistance. CPI-induced IFN-γ mediates activation-induced cell death in T cells as an immune-intrinsic mechanism of resistance. In this study, we found that transient block of IFN-γ signaling through administration of the JAK1 inhibitor ABT-317 enhanced antitumor T cell responses with CPI in preclinical models. Importantly, sequential but not concomitant ABT-317 treatment led to significantly reduced toxicity and improved tumor efficacy. Sequential treatment reduced activation-induced T cell death and enhanced expansion of tumor-reactive T cell subsets with increased effector function in vivo and ex vivo. Only CPI in combination with ABT-317 also enhanced memory responses by protecting mice from tumor rechallenge. These results demonstrate that JAK inhibition within a discrete time window following CPI addresses an immune-intrinsic mechanism of therapeutic resistance.

Indexed as

CTLA-4 AntigenImmune Checkpoint InhibitorsJanus Kinase 1Janus Kinase InhibitorsNeoplasmsProgrammed Cell Death 1 ReceptorAminopyridinesAnimalsCell Line, TumorFemaleHumansImidazolesInterferon-gammaMiceMice, Inbred C57BLPyrrolesAminopyridinesCTLA-4 AntigenImidazolesImmune Checkpoint InhibitorsInterferon-gammaJanus Kinase 1Janus Kinase InhibitorspexidartinibProgrammed Cell Death 1 ReceptorPyrrolesCancer immunotherapyCellular immune responseDrug therapyImmunologyOncology

Identifiers

PMID40014402
PMCPMC11981626

What OpenQuestion holds

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Registered trials

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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.