Evidence map›Paper›PMID 36917954›Full record

ArticleCancer cell2023

Tumor PD-L1 engages myeloid PD-1 to suppress type I interferon to impair cytotoxic T lymphocyte recruitment.

John D Klement, Priscilla S Redd, Chunwan Lu, Alyssa D Merting, Dakota B Poschel, Dafeng Yang, Natasha M Savage, Gang Zhou, David H Munn, Padraic G Fallon and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 2 pooled it
27.2field-weighted citation impact, top 1% 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

72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Macrophage Trogocytosis of Tumor Cells Drives the Immunosuppression of Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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12 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 3 countries.

John D KlementDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
Priscilla S ReddDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
Chunwan LuDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
Alyssa D MertingDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
Dakota B PoschelDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
Dafeng YangDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
Natasha M SavageDepartment of Pathology, Medical College of Georgia, Augusta, GA 30912, USA.
Gang ZhouGeorgia Cancer Center, Augusta, GA 30912, USA.
David H MunnGeorgia Cancer Center, Augusta, GA 30912, USA.
Padraic G FallonTrinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland.
Kebin LiuDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA. Electronic address: kliu@augusta.edu.
National Cancer Center of Georgia · GEAugusta University · USCharlie Norwood VA Medical Center · USTrinity College Dublin · IE

Funding

Reprogramming the TME for immunogenic antigen-presentationR01CA103320 · NCI · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MUNN, DAVID H. · 2003 to 2024
$6.0M
Role of IRF8 in Tumor Rejection and SuppressionR01CA133085 · NCI · AUGUSTA UNIVERSITY · PI LIU, KEBIN · 2008 to 2019
$2.9M
TUMOR SPECIFIC DELIVERY OF VERTICILLIN A OVERCOMES EPIGENETIC SILENCING RESPONSIBLE FOR DRUG RESISTANCER01CA227433 · NCI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI COLSON, YOLONDA L, GRINSTAFF, MARK W. · 2018 to 2022
$2.7M
Persistent STAT5 signaling in polyfunctional CD4 T cells and its application in adoptive T cell therapyR01CA264983 · NCI · AUGUSTA UNIVERSITY · PI SHI, HUIDONG, ZHOU, GANG · 2021 to 2025
$2.6M
Exploiting the immunomodulatory effects of sulindac and novel non-COX inhibitory derivatives for cancer treatmentR01CA238514 · NCI · AUGUSTA UNIVERSITY · PI PIAZZA, GARY A, ZHOU, GANG · 2020 to 2024
$2.1M
PTEN, Tregs and MDSCs in the tumor microenvironmentR01CA211229 · NCI · AUGUSTA UNIVERSITY · PI MUNN, DAVID H. · 2017 to 2021
$1.7M
Function of IRF8 in T cell activation and immune toleranceF30CA236436 · NCI · AUGUSTA UNIVERSITY · PI KLEMENT, JOHN DAVID · 2019 to 2022
$185k
Epigenetic regulation of myeloid regulatory cell accumulation in the tumor microenvironmentF31CA257212 · NCI · AUGUSTA UNIVERSITY · PI MERTING, ALYSSA · 2021 to 2022
$81k
ShEEP-IC: Request for Flow CytometerIS1BX004009 · VA · CHARLIE NORWOOD VA MEDICAL CENTER · PI LIU, KEBIN · 2017 to 2017
–
Type I Interferon Regulation of Tumor Cell and Immune Cell Interaction in Human Colon CancerI01CX001364 · VA · CHARLIE NORWOOD VA MEDICAL CENTER · PI KEBIN LIU · 2019 to 2026
–
BLRD VA IS1 BX004009CSRD VA I01 CX001364NCI NIH HHS F30 CA236436NCI NIH HHS F31 CA257212NCI NIH HHS R01 CA103320NCI NIH HHS R01 CA133085NCI NIH HHS R01 CA211229NCI NIH HHS R01 CA227433NCI NIH HHS R01 CA238514NCI NIH HHS R01 CA264983
6 · The paper itself

Abstract

The cellular and molecular mechanisms underlying tumor cell PD-L1 (tPD-L1) function in tumor immune evasion are incompletely understood. We report here that tPD-L1 does not suppress cytotoxic T lymphocyte (CTL) activity in co-cultures of tumor cells and tumor-specific CTLs and exhibits no effect on primary tumor growth. However, deleting tPD-L1 decreases lung metastasis in a CTL-dependent manner in tumor-bearing mice. Depletion of myeloid cells or knocking out PD-1 in myeloid cells (mPD-1) impairs tPD-L1 promotion of tumor lung metastasis in mice. Single-cell RNA sequencing (scRNA-seq) reveals that tPD-L1 engages mPD-1 to activate SHP2 to antagonize the type I interferon (IFN-I) and STAT1 pathway to repress Cxcl9 and impair CTL recruitment to lung metastases. Human cancer patient response to PD-1 blockade immunotherapy correlates with IFN-I response in myeloid cells. Our findings determine that tPD-L1 engages mPD-1 to activate SHP2 to suppress the IFN-I-STAT1-CXCL9 pathway to impair CTL tumor recruitment in lung metastasis.

Indexed as

Interferon Type ILung NeoplasmsAnimalsB7-H1 AntigenCell Line, TumorHumansMiceProgrammed Cell Death 1 ReceptorT-Lymphocytes, CytotoxicB7-H1 AntigenInterferon Type IProgrammed Cell Death 1 ReceptorCTLCXCL9immune checkpoint blockadelung metastasisPD-1PD-L1SHP2type I interferon

Identifiers

PMID36917954
PMCPMC10150625
OpenAlexW4324046192

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.