Evidence map›Paper›PMID 35366939›Full record

ArticleJournal of experimental & clinical cancer research : CR2022

Differential responses to immune checkpoint inhibitor dictated by pre-existing differential immune profiles in squamous cell carcinomas caused by same initial oncogenic drivers.

Samantha M Y Chen, Vince Popolizio, Rachel A Woolaver, Huaibin Ge, Alexandra L Krinsky, Jessy John, Etienne Danis, Yao Ke, Yonatan Kramer, Li Bian and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

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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

16 authors at 3 institutions in 1 country.

Samantha M Y ChenDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Vince PopolizioDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Rachel A WoolaverDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Huaibin GeUPMC Hillman Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Alexandra L KrinskyDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Jessy JohnUPMC Hillman Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Etienne DanisDepartment of Pharmacology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Yao KeDepartment of Pathology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Yonatan KramerDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Li BianDepartment of Pathology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Andrew G NicklawskyDepartment of Pediatrics and Department of Biostatistics and Informatics, Cancer Center Biostatistics Core, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Dexiang GaoDepartment of Pediatrics and Department of Biostatistics and Informatics, Cancer Center Biostatistics Core, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA.
Silvia LiuDepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Zhangguo ChenUPMC Hillman Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Xiao-Jing WangDepartment of Pathology, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO, 80045, USA. xj.wang@cuanschutz.edu.
Jing H WangUPMC Hillman Cancer Center, Division of Hematology and Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA. JHW51@pitt.edu.
University of Colorado Anschutz Medical Campus · USUPMC Hillman Cancer Center · USUniversity of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
TRAINING PROGRAM IN IMMUNOLOGYT32AI007405 · NIAID · UNIVERSITY OF COLORADO DENVER · PI Laurel L Lenz, Raul Martin Torres · 1991 to 2026
$10.5M
Training in Translational Research of Lung, Head and Neck CancerT32CA174648 · NCI · UNIVERSITY OF COLORADO DENVER · PI KARAM, SANA D · 2013 to 2022
$4.2M
Identifying cellular and molecular signatures from distinct T cell receptor clonotypes associated with favorable immune checkpoint inhibitor responses in HNSCCsR01DE031947 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Robert L. Ferris, Lazar Vujanovic · 2022 to 2026
$3.6M
Elucidating Mechanism of Immune Evasion in Head and Neck CancersR01DE027329 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WANG, JING HONG, WANG, XIAO-JING · 2018 to 2022
$2.8M
Mechanisms of Dual Inhibition of TGFbeta/PD-L1 in HNSCCR01DE028420 · NIDCR · UNIVERSITY OF COLORADO DENVER · PI WANG, JING HONG, WANG, XIAO-JING · 2019 to 2023
$2.7M
Mechanisms underlying therapy failure of immune checkpoint inhibitors and Notch1 loss-mediated immunosuppression in head and neck cancersF31DE027854 · NIDCR · UNIVERSITY OF COLORADO DENVER · PI WOOLAVER, RACHEL A · 2018 to 2020
$100k
Mechanisms of Breaking Indolence in Squamous Cell CarcinomaI01BX003232 · VA · VA NORTHERN CALIFORNIA HEALTH CARE SYS · PI WANG, XIAO-JING · 2017 to 2025
–
BLRD VA I01 BX003232BLRD VA IK6 BX006039NCI NIH HHS P30 CA046934NCI NIH HHS P30CA046934NCI NIH HHS P30 CA047904NCI NIH HHS T32 CA174648NIAID NIH HHS T32 AI007405NIDCR NIH HHS F31 DE027854NIDCR NIH HHS R01 DE027329NIDCR NIH HHS R01 DE028420NIDCR NIH HHS R01 DE031947NIDCR NIH HHS R01DE031947NIH HHS F31DE027854NIH HHS R01-DE027329NIH HHS R01-DE028420NIH HHS T32CA174648
6 · The paper itself

Abstract

backgroundWhile immune checkpoint inhibitors (ICI) were approved for head and neck squamous cell carcinomas (HNSCCs), the response rate remains relatively low. Mechanisms underlying ICI unresponsiveness versus sensitivity are not fully understood.

methodTo better delineate differential responses to ICI treatment, we employed mouse SCC models, termed KPPA tumors that were caused by deleting p53 and hyperactivating PIK3CA, two most frequently mutated genes in human HNSCCs. We transplanted two KPPA tumor lines (TAb2 versus TCh3) into C57BL/6 recipients and examined the immune tumor microenvironment using flow cytometry. Furthermore, we employed single-cell RNA sequencing to identify the difference in tumor infiltrating lymphocytes (TILs).

resultsWe found that different KPPA tumors exhibited heterogeneous immune profiles pre-existing treatment that dictated their sensitivity or unresponsiveness to anti-PD-L1. Unresponsive TAb2 tumors were highly enriched with functional tumor-associated macrophages (TAMs), especially M2-TAMs. In contrast, sensitive TCh3 tumors contained more CD8 TILs with better effector functions. TAb2 tumor cells drastically expanded F4/80

conclusionsWe uncovered tumor-intrinsic differences that may underlie the differential responses to ICI by establishing and employing two SCC tumor lines, TAb2 vs. TCh3, both of which harbor TP53 deletion and PIK3CA hyperactivation. Our study indicates the limitation of stratifying cancers according to their genetic alterations and suggests that evaluating HNSCC tumor-intrinsic cues along with immune profiles in the TME may help better predict ICI responses. Our experimental models may provide a platform for pinpointing tumor-intrinsic differences underlying an immunosuppressive TME in HNSCCs and for testing combined immunotherapies targeting either tumor-specific or TAM-specific players to improve ICI efficacy.

Indexed as

Carcinoma, Squamous CellHead and Neck NeoplasmsAnimalsHumansImmune Checkpoint InhibitorsMiceMice, Inbred C57BLOncogenesTumor MicroenvironmentImmune Checkpoint InhibitorsCancer immunotherapyHead and neck cancersImmune tumor microenvironmentp53 mutationsPIK3CA hyperactivationTumor infiltrating lymphocytes

Identifiers

PMID35366939
PMCPMC8976353
OpenAlexW4226031585

What Socratic holds

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LicenceCC BY
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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 Socratic graph.