Characterization of the immune response in patients with cancer of the oral cavity after neoadjuvant immunotherapy with the IRX-2 regimen.
Cytokine
Immunotherapy
NanoString
Neoadjuvant
Oral cavity carcinoma
Tumor infiltrating lymphocytes
Journal
Oral oncology
ISSN: 1879-0593
Titre abrégé: Oral Oncol
Pays: England
ID NLM: 9709118
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
12
07
2021
revised:
26
09
2021
accepted:
15
10
2021
pubmed:
31
10
2021
medline:
11
3
2022
entrez:
30
10
2021
Statut:
ppublish
Résumé
IRX-2 is a homologous cell-derived multi-cytokine biologic with multifaceted immune modulatory effects that has been shown to induce increased lymphocyte infiltration into primary tumors in oral cavity carcinoma. Our objective was to characterize tumor immune gene expression and epigenomic changes after neoadjuvant IRX-2 immunotherapy in patients with squamous cell carcinoma of the oral cavity. A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery for previously untreated patients with Stage II-IV oral cavity carcinoma. The treatment regimen consisted of low dose (300 mg/m A total of 51 and 79 immune-related genes were found upregulated and downregulated, respectively, in the samples from Regimen 1 patients after treatment, while 51 and 56 were found upregulated and downregulated in the samples for Regimen 2. When comparing the changes between the two regimens, we identified 9 genes significantly different, including DMBT1, a potential tumor suppressor, functioning in tumor invasion of head and neck cancer. The exploration of DNA methylation showed slight overall hypermethylation after treatment in both regimens, especially for Regimen 1 immune responders, and methylation-based cell type deconvolution demonstrated high concordance with tumor infiltrating T lymphocyte cell counts. While a consistent patient response after treatment was observed, most changes were similar between regimens, indicating a subtle, targeted, or patient-specific effect of IRX-2 cytokines. Change in DMBT1 expression was a unique finding that will require further study to better understand its significance.
Identifiants
pubmed: 34717154
pii: S1368-8375(21)00694-1
doi: 10.1016/j.oraloncology.2021.105587
pmc: PMC8982160
mid: NIHMS1789439
pii:
doi:
Substances chimiques
Calcium-Binding Proteins
0
Cytokines
0
DMBT1 protein, human
0
DNA-Binding Proteins
0
IRX 2
0
Tumor Suppressor Proteins
0
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105587Subventions
Organisme : NCI NIH HHS
ID : P01 CA240239
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046592
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES017885
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA250214
Pays : United States
Investigateurs
Jeff Moyer
(J)
Mihir Patel
(M)
Audrey Erman
(A)
Wanessa A Martins
(WA)
Jason Newman
(J)
Michael Kaplan
(M)
Frabicio Oliveira
(F)
Ana Paula Victorina
(AP)
R Bryan Bell
(R)
Gustavo C Girotto
(GC)
Jorge Nieva
(J)
Joseph Valentino
(J)
Greg Krempl
(G)
Claudio R Cernea
(CR)
Dennis Kraus
(D)
Kevin Higgins
(K)
Felipe J S M Cruz
(FJSM)
Aru Panwar
(A)
Clodoaldo Z Campos
(CZ)
Jim McCaul
(J)
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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