Evidence map›Paper›PMID 30737146›Full record

ArticleImmunity2019

Clonal Deletion of Tumor-Specific T Cells by Interferon-γ Confers Therapeutic Resistance to Combination Immune Checkpoint Blockade.

Chien-Chun Steven Pai, John T Huang, Xiaoqing Lu, Donald M Simons, Chanhyuk Park, Anthony Chang, Whitney Tamaki, Eric Liu, Kole T Roybal, Jane Seagal and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% of its field
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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. CXCL12 upregulates PD-L1 expression and promotes M2 polarisation of tumour-associated macrophages to confer anti-PD-1 resistance in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Article
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  11. Fanning the flames: IFN-γ fuels CAR-T inflammation and cytopenia.The Journal of clinical investigation · 2026
    Article
  12. Review
  13. Article
  14. The diversity of CD8Nature reviews. Immunology · 2025
    Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. A Spatially Distributed Microneedle System for Bioorthogonal T Cell-Guided Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  20. Article

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 3 institutions in 1 country.

Chien-Chun Steven PaiDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
John T HuangDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
Xiaoqing LuAbbVie Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA.
Donald M SimonsAbbVie Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA.
Chanhyuk ParkDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
Anthony ChangDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
Whitney TamakiDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
Eric LiuDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
Kole T RoybalHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Jane SeagalAbbVie Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA.
Mingyi ChenDepartment of Hematopathology, School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Katsunobu HagiharaDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Xiao X WeiDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Michel DuPageHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Serena S KwekDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
David Y OhDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Adil DaudDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Katy K TsaiDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Clint WuDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Li ZhangDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Marcella FassoDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
Ravi SachidanandamGirihlet, 355 30th Street, Oakland, CA 94609, USA.
Anitha JayaprakashGirihlet, 355 30th Street, Oakland, CA 94609, USA.
Ingrid LinDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Amy-Jo CasbonDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
Gillian A KinsburyAbbVie Bioresearch Center, 100 Research Drive, Worcester, MA 01605, USA.
Lawrence FongDepartment of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: lawrence.fong@ucsf.edu.
University of California, San Francisco · USAbbVie (United States) · USThe University of Texas Southwestern Medical Center · US

Funding

Molecular and immune drivers of immunotherapy responsiveness in prostate cancerU01CA233100 · NCI · DANA-FARBER CANCER INST · PI FONG, LAWRENCE, VAN ALLEN, ELIEZER M · 2018 to 2022
$4.2M
Immunotherapy of human bladder cancerR01CA194511 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FONG, LAWRENCE · 2015 to 2019
$2.1M
Prostatitis and Prostate Cancer DevelopmentR01CA163012 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FONG, LAWRENCE · 2012 to 2016
$2.0M
Determinants of prostate cancer sensitivity to PD-1 blockadeR01CA223484 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FONG, LAWRENCE · 2018 to 2021
$1.1M
NCI NIH HHS R01 CA163012NCI NIH HHS R01 CA194511NCI NIH HHS R01 CA223484NCI NIH HHS U01 CA233100
6 · The paper itself

Abstract

Resistance to checkpoint-blockade treatments is a challenge in the clinic. We found that although treatment with combined anti-CTLA-4 and anti-PD-1 improved control of established tumors, this combination compromised anti-tumor immunity in the low tumor burden (LTB) state in pre-clinical models as well as in melanoma patients. Activated tumor-specific T cells expressed higher amounts of interferon-γ (IFN-γ) receptor and were more susceptible to apoptosis than naive T cells. Combination treatment induced deletion of tumor-specific T cells and altered the T cell repertoire landscape, skewing the distribution of T cells toward lower-frequency clonotypes. Additionally, combination therapy induced higher IFN-γ production in the LTB state than in the high tumor burden (HTB) state on a per-cell basis, reflecting a less exhausted immune status in the LTB state. Thus, elevated IFN-γ secretion in the LTB state contributes to the development of an immune-intrinsic mechanism of resistance to combination checkpoint blockade, highlighting the importance of achieving the optimal magnitude of immune stimulation for successful combination immunotherapy strategies.

Indexed as

AnimalsAntibodies, MonoclonalCell Line, TumorClonal DeletionCTLA-4 AntigenDrug Resistance, NeoplasmHumansInterferon-gammaMaleMice, Inbred C57BLMice, KnockoutNeoplasms, ExperimentalProgrammed Cell Death 1 ReceptorT-LymphocytesTumor BurdenAntibodies, MonoclonalCTLA-4 AntigenCTLA4 protein, humanInterferon-gammaProgrammed Cell Death 1 Receptoractivation-induced cell deathanti-CTLA-4anti-PD-1cancerIFN-γimmunotherapy

Identifiers

PMID30737146
PMCPMC6886475
OpenAlexW2913142277

What OpenQuestion holds

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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 OpenQuestion graph.