Immunological and Genetic Characterization of Patients With Head and Neck Cancer who Developed Recurrence.

Epithelial-Mesenchymal Transition / genetics Head and Neck Neoplasms / genetics Humans Papillomaviridae Squamous Cell Carcinoma of Head and Neck / genetics Transforming Growth Factor beta1 Tumor Microenvironment / genetics
TP53 mutation-TGF-β1-PAX7 pathway Tumor microenvironment (TME) epithelial-mesenchymal transition human papillomavirus tumor-infiltrating lymphocytes

Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Sep 2022
Historique:
received: 01 06 2022
revised: 05 07 2022
accepted: 06 07 2022
entrez: 30 8 2022
pubmed: 31 8 2022
medline: 1 9 2022
Statut: ppublish

Résumé

The recurrence rate of head and neck squamous cell carcinoma (HNSCC) remains high; thus the control of recurrence is a clinical problem to be challenged. To clarify the precise mechanism, specific immunological biomarkers responsible for recurrence were investigated. The expression levels of immune response-associated and Shizuoka Cancer Center 820 cancer-associated genes, and genetic mutations from whole-exome sequencing were compared between HNSCC patients who developed recurrence (n=8) and HNSCC patients who did not develop recurrence (n=19) using a volcano plot analysis. Cytokine and epithelial-mesenchymal transition marker genes were analyzed using quantitative PCR. Tumor-infiltrating lymphocytes, immune checkpoint molecules, and human papilloma virus status were investigated using immunohistochemistry (IHC). Twenty-seven evaluable patients with HNSCCs received radiation therapy after surgery. Recurrence was identified in 8 patients. TP53 mutations tended to be higher in patients who developed recurrence than in those who did not develop recurrence (75% vs. 31.6%). Gene expression profiling showed the down-regulation of T cell activation genes (ICOS, CD69 and CD83) and the upregulation of the ERBB4, EGFR, VEGF, HIF1A, TGFB1, TWIST1, IL-8, and PAX7 genes, which suggested the activation of the TP53 mutation-TGF-β1-PAX7 pathway and epithelial-mesenchymal transition. Additionally, IHC indicated a tendency toward a reduction in T cell accumulation and an increase in M2-type macrophage infiltration in tumors that recurred. A TP53 mutation-mediated immune-suppressive state in the tumor microenvironment and TGF-β1-PAX7-mediated EMT might contribute to the promotion of recurrence in patients with HNSCC after postoperative radiotherapy.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
The recurrence rate of head and neck squamous cell carcinoma (HNSCC) remains high; thus the control of recurrence is a clinical problem to be challenged. To clarify the precise mechanism, specific immunological biomarkers responsible for recurrence were investigated.
PATIENTS AND METHODS METHODS
The expression levels of immune response-associated and Shizuoka Cancer Center 820 cancer-associated genes, and genetic mutations from whole-exome sequencing were compared between HNSCC patients who developed recurrence (n=8) and HNSCC patients who did not develop recurrence (n=19) using a volcano plot analysis. Cytokine and epithelial-mesenchymal transition marker genes were analyzed using quantitative PCR. Tumor-infiltrating lymphocytes, immune checkpoint molecules, and human papilloma virus status were investigated using immunohistochemistry (IHC).
RESULTS RESULTS
Twenty-seven evaluable patients with HNSCCs received radiation therapy after surgery. Recurrence was identified in 8 patients. TP53 mutations tended to be higher in patients who developed recurrence than in those who did not develop recurrence (75% vs. 31.6%). Gene expression profiling showed the down-regulation of T cell activation genes (ICOS, CD69 and CD83) and the upregulation of the ERBB4, EGFR, VEGF, HIF1A, TGFB1, TWIST1, IL-8, and PAX7 genes, which suggested the activation of the TP53 mutation-TGF-β1-PAX7 pathway and epithelial-mesenchymal transition. Additionally, IHC indicated a tendency toward a reduction in T cell accumulation and an increase in M2-type macrophage infiltration in tumors that recurred.
CONCLUSION CONCLUSIONS
A TP53 mutation-mediated immune-suppressive state in the tumor microenvironment and TGF-β1-PAX7-mediated EMT might contribute to the promotion of recurrence in patients with HNSCC after postoperative radiotherapy.

Identifiants

DOI: 10.21873/anticanres.15942 PMID: 36039416
pubmed: 36039416
pii: 42/9/4417
doi: 10.21873/anticanres.15942
doi:

Substances chimiques

Transforming Growth Factor beta1 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4417-4428

Informations de copyright

Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Kazuaki Yasui (K)

Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Ryota Kondou (R)

Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

Haruo Miyata (H)

Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

Akira Iizuka (A)

Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

Tadashi Ashizawa (T)

Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

Takeshi Nagashima (T)

Cancer Diagnostic Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
SRL Inc., Tokyo, Japan.

Keiichi Ohshima (K)

Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

Kenichi Urakami (K)

Cancer Diagnostic Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

Koji Muramatsu (K)

Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Takashi Sugino (T)

Division of Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Ken Yamaguchi (K)

Office of the President, Shizuoka Cancer Center, Shizuoka, Japan.

Hirofumi Ogawa (H)

Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Tsuyoshi Onoe (T)

Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Hideyuki Harada (H)

Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Hirofumi Asakura (H)

Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Shigeyuki Murayama (S)

Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Tetsuo Nishimura (T)

Radiation and Proton Therapy Center, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Seiya Goto (S)

Division of Head and Neck Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Shinichi Okada (S)

Division of Head and Neck Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Takashi Mukaigawa (T)

Division of Head and Neck Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Satoshi Hamauchi (S)

Division of Gastrointestinal Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Tomoya Yokota (T)

Division of Gastrointestinal Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Yusuke Onozawa (Y)

Division of Clinical Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Yasuto Akiyama (Y)

Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan; y.akiyama@scchr.jp.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transdifférenciation cellulaire › Transition épithélio-mésenchymateuse › Immunological and Genetic Characterization of...
questionsmedicales.fr › Tumeurs › Tumeurs par siège › Tumeurs de la tête et du cou › Immunological and Genetic Characterization of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Immunological and Genetic Characterization of...
questionsmedicales.fr › Virus › Virus oncogènes › Virus tumoraux à ADN › Papillomaviridae › Immunological and Genetic Characterization of...
questionsmedicales.fr › Tumeurs › Tumeurs par siège › Tumeurs de la tête et du cou › Carcinome épidermoïde de la tête et du cou › Immunological and Genetic Characterization of...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la superfamille du TGF bêta › Facteur de croissance transformant bêta › Facteur de croissance transformant bêta-1 › Immunological and Genetic Characterization of...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Immunological and Genetic Characterization of...