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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2025
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| _version_ | 1849927624466366464 |
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| 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 |