Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg

Introduction<p>Oropharyngeal squamous cell carcinoma (OPC) associated with high-risk human papillomavirus (HPV), particularly HPV-16, generally shows favorable outcomes yet paradoxically exhibits a high incidence of early lymphatic metastasis. The immune mechanisms underlying this phenomenon r...

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সংরক্ষণ করুন:
গ্রন্থ-পঞ্জীর বিবরন
প্রধান লেখক: Naohiro Wakisaka (407153) (author)
অন্যান্য লেখক: Makiko Moriyama-Kita (833101) (author), Satoru Kondo (407152) (author), Eiji Kobayashi (107710) (author), Takayoshi Ueno (457816) (author), Yosuke Nakanishi (407151) (author), Kazuhira Endo (407155) (author), Hisashi Sugimoto (2146888) (author), Tomokazu Yoshizaki (407160) (author)
প্রকাশিত: 2025
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_version_ 1849927624466366464
author Naohiro Wakisaka (407153)
author2 Makiko Moriyama-Kita (833101)
Satoru Kondo (407152)
Eiji Kobayashi (107710)
Takayoshi Ueno (457816)
Yosuke Nakanishi (407151)
Kazuhira Endo (407155)
Hisashi Sugimoto (2146888)
Tomokazu Yoshizaki (407160)
author2_role author
author
author
author
author
author
author
author
author_facet Naohiro Wakisaka (407153)
Makiko Moriyama-Kita (833101)
Satoru Kondo (407152)
Eiji Kobayashi (107710)
Takayoshi Ueno (457816)
Yosuke Nakanishi (407151)
Kazuhira Endo (407155)
Hisashi Sugimoto (2146888)
Tomokazu Yoshizaki (407160)
author_role author
dc.creator.none.fl_str_mv Naohiro Wakisaka (407153)
Makiko Moriyama-Kita (833101)
Satoru Kondo (407152)
Eiji Kobayashi (107710)
Takayoshi Ueno (457816)
Yosuke Nakanishi (407151)
Kazuhira Endo (407155)
Hisashi Sugimoto (2146888)
Tomokazu Yoshizaki (407160)
dc.date.none.fl_str_mv 2025-11-26T05:14:47Z
dc.identifier.none.fl_str_mv 10.3389/fonc.2025.1732480.s001
dc.relation.none.fl_str_mv https://figshare.com/articles/figure/Image_5_Exploratory_spatial_transcriptomic_profiling_of_peritumoral_Th2_immune_polarization_in_HPV-positive_oropharyngeal_cancer_jpeg/30717554
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Oncology and Carcinogenesis not elsewhere classified
HPV-positive oropharyngeal cancer
palatine tonsil
spatial transcriptomics
tumor immune microenvironment
Th2 immunity
lymphatic metastasis
eosinophils and mast cells
estrogen signaling
dc.title.none.fl_str_mv Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg
dc.type.none.fl_str_mv Image
Figure
info:eu-repo/semantics/publishedVersion
image
description Introduction<p>Oropharyngeal squamous cell carcinoma (OPC) associated with high-risk human papillomavirus (HPV), particularly HPV-16, generally shows favorable outcomes yet paradoxically exhibits a high incidence of early lymphatic metastasis. The immune mechanisms underlying this phenomenon remain unclear.</p>Methods<p>We conducted an exploratory spatial transcriptomic analysis using the GeoMx Digital Spatial Profiler on formalin-fixed, paraffin-embedded samples from six patients with palatine tonsil-derived OPC. Tumor tissue regions (TTRs) and lymphoid follicular regions (LFRs) were compared according to HPV status and nodal involvement.</p>Results<p>In HPV-positive LFRs, pathways related to B-cell apoptosis appeared downregulated, suggesting prolonged B-cell survival and antigen presentation. Metastasis-negative HPV-positive cases displayed a Th2-skewed immune profile in LFRs, with increased naïve B cells, plasma cells, eosinophils, M2 macrophages, and activated mast cells. In contrast, metastasis-positive cases showed increased T cell activation in LFRs and reduced proliferation-related signaling in TTRs. Pathways involving estrogen signaling and bile acid metabolism were also associated with metastatic behavior.</p>Conclusion<p>These exploratory findings suggest that peritumoral Th2-biased immunity within lymphoid structures may contribute to restraining lymphatic metastasis in HPV-positive OPC. Spatial transcriptomics may provide a high-resolution framework for investigating tumor–immune interactions and generating hypotheses for future mechanistic and clinical studies.</p>
eu_rights_str_mv openAccess
id Manara_a8e1eece3e0423ae5203ac7a542cd956
identifier_str_mv 10.3389/fonc.2025.1732480.s001
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/30717554
publishDate 2025
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpegNaohiro Wakisaka (407153)Makiko Moriyama-Kita (833101)Satoru Kondo (407152)Eiji Kobayashi (107710)Takayoshi Ueno (457816)Yosuke Nakanishi (407151)Kazuhira Endo (407155)Hisashi Sugimoto (2146888)Tomokazu Yoshizaki (407160)Oncology and Carcinogenesis not elsewhere classifiedHPV-positive oropharyngeal cancerpalatine tonsilspatial transcriptomicstumor immune microenvironmentTh2 immunitylymphatic metastasiseosinophils and mast cellsestrogen signalingIntroduction<p>Oropharyngeal squamous cell carcinoma (OPC) associated with high-risk human papillomavirus (HPV), particularly HPV-16, generally shows favorable outcomes yet paradoxically exhibits a high incidence of early lymphatic metastasis. The immune mechanisms underlying this phenomenon remain unclear.</p>Methods<p>We conducted an exploratory spatial transcriptomic analysis using the GeoMx Digital Spatial Profiler on formalin-fixed, paraffin-embedded samples from six patients with palatine tonsil-derived OPC. Tumor tissue regions (TTRs) and lymphoid follicular regions (LFRs) were compared according to HPV status and nodal involvement.</p>Results<p>In HPV-positive LFRs, pathways related to B-cell apoptosis appeared downregulated, suggesting prolonged B-cell survival and antigen presentation. Metastasis-negative HPV-positive cases displayed a Th2-skewed immune profile in LFRs, with increased naïve B cells, plasma cells, eosinophils, M2 macrophages, and activated mast cells. In contrast, metastasis-positive cases showed increased T cell activation in LFRs and reduced proliferation-related signaling in TTRs. Pathways involving estrogen signaling and bile acid metabolism were also associated with metastatic behavior.</p>Conclusion<p>These exploratory findings suggest that peritumoral Th2-biased immunity within lymphoid structures may contribute to restraining lymphatic metastasis in HPV-positive OPC. Spatial transcriptomics may provide a high-resolution framework for investigating tumor–immune interactions and generating hypotheses for future mechanistic and clinical studies.</p>2025-11-26T05:14:47ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.3389/fonc.2025.1732480.s001https://figshare.com/articles/figure/Image_5_Exploratory_spatial_transcriptomic_profiling_of_peritumoral_Th2_immune_polarization_in_HPV-positive_oropharyngeal_cancer_jpeg/30717554CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307175542025-11-26T05:14:47Z
spellingShingle Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg
Naohiro Wakisaka (407153)
Oncology and Carcinogenesis not elsewhere classified
HPV-positive oropharyngeal cancer
palatine tonsil
spatial transcriptomics
tumor immune microenvironment
Th2 immunity
lymphatic metastasis
eosinophils and mast cells
estrogen signaling
status_str publishedVersion
title Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg
title_full Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg
title_fullStr Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg
title_full_unstemmed Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg
title_short Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg
title_sort Image 5_Exploratory spatial transcriptomic profiling of peritumoral Th2 immune polarization in HPV-positive oropharyngeal cancer.jpeg
topic Oncology and Carcinogenesis not elsewhere classified
HPV-positive oropharyngeal cancer
palatine tonsil
spatial transcriptomics
tumor immune microenvironment
Th2 immunity
lymphatic metastasis
eosinophils and mast cells
estrogen signaling