Evidence map›Paper›PMID 40475776›Full record

ArticleFrontiers in immunology2025

CBD promotes antitumor activity by modulating tumor immune microenvironment in HPV associated head and neck squamous cell carcinoma.

Prakriti Sen, Sayed Sadat, Koji Ebisumoto, Riyam Al-Msari, Sayuri Miyauchi, Souvick Roy, Pardis Mohammadzadeh, Kristin Lips, Takuya Nakagawa, Robert Saddawi-Konefka and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
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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

12 authors.

Prakriti SenGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
Sayed SadatGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
Koji EbisumotoGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
Riyam Al-MsariGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
Sayuri MiyauchiDepartment of Radiation Medicine and Applied Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.
Souvick RoyDepartment of Radiation Medicine and Applied Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.
Pardis MohammadzadehGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
Kristin LipsGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
Takuya NakagawaGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
Robert Saddawi-KonefkaDepartment of Otolaryngology-Head and Neck Surgery, Moores Cancer Center, University of California San Diego Health, La Jolla, CA, United States.
Andrew B SharabiDepartment of Radiation Medicine and Applied Sciences, Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.
Joseph A CalifanoGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
NCI NIH HHS P30 CA023100
6 · The paper itself

Abstract

Introduction: Marijuana use is associated with HPV-positive head and neck squamous cell carcinoma (HNSCC). However, cannabinoid use continues to increase in the US general population for recreational purposes as well as in cancer patients for palliative care. In this study, we explored the role of cannabidiol (CBD) in promoting anti-tumor activity by modulating immune response in HPV-positive HNSCC by using pre-clinical models. Methods: The anti-proliferative effect of CBD on HPV-positive HNSCC cells was evaluated through BrdU, apoptosis and migration analyses, followed by western blot analysis to assess its role in activating the MAPK pathway. Next, the anti-tumor immune response of CBD was evaluated in immunocompetent syngeneic mouse as well as in immune-deficient B6.129S7-Rag1 Results: We observed CBD treatment inhibited cell proliferation and migration by promoting apoptosis in HPV-positive HNSCC cells through activation of the MAPK pathway and its associated markers like ERK1/2, JNK/SAPK and MK2. CBD significantly inhibited tumor growth in immunocompetent mice but had no effect in immune-deficient models, indicating an immune-dependent mechanism. CBD enhanced infiltration of CD4+T and CD8+T cells, CD19+B cells, NK cells, and M1-like macrophages into the primary tumors of immunocompetent syngeneic mice models, implicating an enhanced anti-tumor immune response. Interestingly, we observed a significant increase in tumor volume in CD4-depleted mice treated with CBD as compared to CBD-treated wild-type mice suggesting the importance of CD4+T cells in CBD-mediated anti-tumor activity. Finally, multiplex IHC analysis demonstrated co-localization of CD4+T and CD8+ T cells with the activated MAPK marker phospho-p38 in CBD-treated tumors. Discussion: CBD inhibits tumor cell proliferation in HPV-positive HNSCC by activating the MAPK pathway. It also enhances anti-tumor activity by modulating the tumor immune microenvironment, promoting co-localization of p38 MAPK-activated CD4+ and CD8+ T cells.

Indexed as

Antineoplastic AgentsCannabidiolHead and Neck NeoplasmsPapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckTumor MicroenvironmentAnimalsApoptosisCell Line, TumorCell ProliferationFemaleHumansLymphocytes, Tumor-InfiltratingMiceMice, KnockoutMice, NudeAntineoplastic AgentsCannabidiolanti-tumor immune responsecannabinoidCD4+T cellsCD8+T cellsHPV-positive HNSCCMAPK

Identifiers

PMID40475776
PMCPMC12137345

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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.