دورية أكاديمية
أعرض في EDS

Intratumor childhood vaccine-specific CD4 + T-cell recall coordinates antitumor CD8 + T cells and eosinophils.

التفاصيل البيبلوغرافية
العنوان: Intratumor childhood vaccine-specific CD4 + T-cell recall coordinates antitumor CD8 + T cells and eosinophils.
المؤلفون: Brown MC; Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA mcb52@duke.edu., Beasley GM; Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA., McKay ZP; Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA., Yang Y; Department of Neurosurgery, University of Alabama Division of Neurosurgery, Birmingham, Alabama, USA., Desjardins A; Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA., Randazzo DM; Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA., Landi D; Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA., Ashley DM; Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA., Bigner DD; Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA., Nair SK; Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA., Gromeier M; Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA.
المصدر: Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Apr; Vol. 11 (4).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Print Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd.
Original Publication: London : BioMed Central, 2013-
مواضيع طبية MeSH: Tetanus* , Vaccines*, Mice ; Humans ; Animals ; CD8-Positive T-Lymphocytes ; Eosinophils ; CD40 Ligand ; Immunity, Innate ; Lymphocytes ; T-Lymphocytes, Regulatory
مستخلص: Background: Antitumor mechanisms of CD4 + T cells remain crudely defined, and means to effectively harness CD4 + T-cell help for cancer immunotherapy are lacking. Pre-existing memory CD4 + T cells hold potential to be leveraged for this purpose. Moreover, the role of pre-existing immunity in virotherapy, particularly recombinant poliovirus immunotherapy where childhood polio vaccine specific immunity is ubiquitous, remains unclear. Here we tested the hypothesis that childhood vaccine-specific memory T cells mediate antitumor immunotherapy and contribute to the antitumor efficacy of polio virotherapy.
Methods: The impact of polio immunization on polio virotherapy, and the antitumor effects of polio and tetanus recall were tested in syngeneic murine melanoma and breast cancer models. CD8 + T-cell and B-cell knockout, CD4 + T-cell depletion, CD4 + T-cell adoptive transfer, CD40L blockade, assessments of antitumor T-cell immunity, and eosinophil depletion defined antitumor mechanisms of recall antigens. Pan-cancer transcriptome data sets and polio virotherapy clinical trial correlates were used to assess the relevance of these findings in humans.
Results: Prior vaccination against poliovirus substantially bolstered the antitumor efficacy of polio virotherapy in mice, and intratumor recall of poliovirus or tetanus immunity delayed tumor growth. Intratumor recall antigens augmented antitumor T-cell function, caused marked tumor infiltration of type 2 innate lymphoid cells and eosinophils, and decreased proportions of regulatory T cells (Tregs). Antitumor effects of recall antigens were mediated by CD4 + T cells, limited by B cells, independent of CD40L, and dependent on eosinophils and CD8 + T cells. An inverse relationship between eosinophil and Treg signatures was observed across The Cancer Genome Atlas (TCGA) cancer types, and eosinophil depletion prevented Treg reductions after polio recall. Pretreatment polio neutralizing antibody titers were higher in patients living longer, and eosinophil levels increased in the majority of patients, after polio virotherapy.
Conclusion: Pre-existing anti-polio immunity contributes to the antitumor efficacy of polio virotherapy. This work defines cancer immunotherapy potential of childhood vaccines, reveals their utility to engage CD4 + T-cell help for antitumor CD8 + T cells, and implicates eosinophils as antitumor effectors of CD4 + T cells.
Competing Interests: Competing interests: MCB, AD, DMA, DDB, SKN, and MG own intellectual property related to Lerapolturev, which has been licensed to Istari Oncology. MCB, AD, MG, and DDB received consultancy fees from Istari Oncology; MG and DDB hold equity in Istari Oncology. All other authors declare they have no competing interests.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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معلومات مُعتمدة: K99 CA263021 United States CA NCI NIH HHS; R00 CA263021 United States CA NCI NIH HHS; R01 NS108773 United States NS NINDS NIH HHS; F32 CA224593 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Adaptive Immunity; CD4-Positive T-Lymphocytes; Immunogenicity, Vaccine; Immunotherapy; Oncolytic Virotherapy
سلسلة جزيئية: ClinicalTrials.gov NCT01491893; NCT02986178; NCT03712358
المشرفين على المادة: 147205-72-9 (CD40 Ligand)
0 (Vaccines)
تواريخ الأحداث: Date Created: 20230418 Date Completed: 20230420 Latest Revision: 20230626
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10124325
DOI: 10.1136/jitc-2022-006463
PMID: 37072349
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-1426
DOI:10.1136/jitc-2022-006463