Evidence map›Paper›PMID 38372707›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024

Targeting Dendritic Cell Dysfunction to Circumvent Anti-PD1 Resistance in Head and Neck Cancer.

Shin Saito, Michihisa Kono, Hoang C B Nguyen, Ann Marie Egloff, Cameron Messier, Patrick Lizotte, Cloud Paweletz, Douglas Adkins, Ravindra Uppaluri

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

13 citing papers in PubMed, 11 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

9 authors at 4 institutions in 1 country.

Shin Saito *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-2912-7868
Michihisa Kono *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-8506-928X
Hoang C B NguyenDepartment of Surgery/Otolaryngology, Brigham and Women's Hospital, Boston, Massachusetts.ORCID 0000-0001-6975-3084
Ann Marie EgloffDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-1182-2793
Cameron MessierDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-2718-6525
Patrick LizotteDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-9510-0036
Cloud PaweletzDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-2287-5663
Douglas AdkinsAlvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.ORCID 0000-0003-3207-8227
Ravindra UppaluriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-5988-6828
Dana-Farber Cancer Institute · USBrigham and Women's Hospital · USDartmouth College · USWashington University in St. Louis · US

Funding

Defining mechanisms of immunotherapy resistance in head and neck squamous cell carcinomasU01DE029188 · NIDCR · DANA-FARBER CANCER INST · PI BARBIE, DAVID A, HADDAD, ROBERT I. · 2019 to 2019
$4.3M
Immunotherapeutic responses to neoantigens in head and neck cancerR01DE027736 · NIDCR · DANA-FARBER CANCER INST · PI UPPALURI, RAVINDRA · 2018 to 2022
$2.9M
NIDCR NIH HHS R01 DE027736NIDCR NIH HHS U01 DE029188
6 · The paper itself

Abstract

purposeNeoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed. EXPERIMENTAL

designWe integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model.

resultsAn aPD1-resistant mouse model showed poor priming in the tumor DLN due to type 1 conventional dendritic cell (cDC1) dysfunction, which correlated with exhausted and poorly responsive antigen-specific T cells. Tumor microenvironment analysis also showed decreased cDC1 in aPD1-resistant tumors compared with sensitive tumors. Following neoadjuvant aPD1 therapy, pathologic responses in patients also positively correlated with baseline transcriptomic cDC1 signatures. In an aPD1-resistant model, intratumoral cDC1 vaccine was sufficient to restore aPD1 response by enhancing T-cell infiltration and increasing antigen-specific responses with improved tumor control. Mechanistically, CCL5 expression significantly correlated with neoadjuvant aPD1 response and enforced expression of CCL5 in an aPD1-resistant model, enhanced cDC1 tumor infiltration, restored antigen-specific responses, and recovered sensitivity to aPD1 treatment.

conclusionsThese data highlight the contribution of tumor-infiltrating cDC1 in HNSCC aPD1 response and approaches to enhance cDC1 infiltration and function that may circumvent aPD1 resistance in patients with HNSCC.

Indexed as

Dendritic CellsDrug Resistance, NeoplasmHead and Neck NeoplasmsSquamous Cell Carcinoma of Head and NeckTumor MicroenvironmentAnimalsAntibodies, Monoclonal, HumanizedCell Line, TumorChemokine CCL5Disease Models, AnimalFemaleHumansImmune Checkpoint InhibitorsMiceNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorAntibodies, Monoclonal, HumanizedChemokine CCL5Immune Checkpoint InhibitorspembrolizumabProgrammed Cell Death 1 Receptor

Identifiers

PMID38372707
PMCPMC11061605
OpenAlexW4391931944

What OpenQuestion holds

Textmetadata
LicenceTDM
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.