Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease
Abstract We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin‐fixed paraffin‐embedd...
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Wiley
2020-07-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.3106 |
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| author | Katie Meehan Connull Leslie Michaela Lucas Angela Jacques Bob Mirzai James Lim Max Bulsara Yasir Khan Nicholas C. Wong Benjamin Solomon Chady Sader Peter Friedland Gisela Mir Arnau Timothy Semple Annette M. Lim |
| author_facet | Katie Meehan Connull Leslie Michaela Lucas Angela Jacques Bob Mirzai James Lim Max Bulsara Yasir Khan Nicholas C. Wong Benjamin Solomon Chady Sader Peter Friedland Gisela Mir Arnau Timothy Semple Annette M. Lim |
| author_sort | Katie Meehan |
| collection | DOAJ |
| description | Abstract We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin‐fixed paraffin‐embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non‐cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD‐L1, and PD‐1 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24‐immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, P < .001 and worse survival for LSCC, P = .038). OTSCC exhibited concordant gene and immunohistochemical (IHC) features characterized by a TH‐2 biased, proinflammatory profile with upregulated B cell and neutrophil gene activity and increased CD4, FOXP3, and PD‐L1 expression (P < .001 for all by IHC). Compared to less advanced disease, nodal involvement and recurrent OTSCC did not induce a different immune response although recurrent disease was characterized by significantly higher PD‐L1 expression (P = .004 by SP263, P = .013 by 22C3, P = .004 for gene expression). Identification of a gene signature associated with different prognostic effects in other cancers highlights common pathways of immune dysregulation that are impacted by the tumor origin. The significant immunosuppressive signaling in OTSCC indicates primary failure of immune system to control carcinogenesis emphasizing the need for early, combination therapeutic approaches. |
| format | Article |
| id | doaj-art-c08ee623e4694fc1995cafcc8f96480a |
| institution | OA Journals |
| issn | 2045-7634 |
| language | English |
| publishDate | 2020-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-c08ee623e4694fc1995cafcc8f96480a2025-08-20T01:58:43ZengWileyCancer Medicine2045-76342020-07-019134791480710.1002/cam4.3106Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing diseaseKatie Meehan0Connull Leslie1Michaela Lucas2Angela Jacques3Bob Mirzai4James Lim5Max Bulsara6Yasir Khan7Nicholas C. Wong8Benjamin Solomon9Chady Sader10Peter Friedland11Gisela Mir Arnau12Timothy Semple13Annette M. Lim14Chinese University of Hong Kong Hong KongDepartment of Anatomical Pathology PathWest Laboratory Medicine Queen Elizabeth Medical Centre Nedlands WA AustraliaUniversity of Western Australia Crawley WA AustraliaInstitute for Health Research University of Notre Dame Fremantle WA AustraliaDepartment of Anatomical Pathology PathWest Laboratory Medicine Queen Elizabeth Medical Centre Nedlands WA AustraliaGenomics WATelethon Kids Institute West Perth WA AustraliaInstitute for Health Research University of Notre Dame Fremantle WA AustraliaDepartment of Medical Oncology Sir Charles Gairdner Hospital Nedlands WA AustraliaMonash Bioinformatics Platform Monash University Clayton VIC AustraliaPeter MacCallum Cancer Centre Melbourne VIC AustraliaUniversity of Western Australia Crawley WA AustraliaUniversity of Western Australia Crawley WA AustraliaPeter MacCallum Cancer Centre Melbourne VIC AustraliaPeter MacCallum Cancer Centre Melbourne VIC AustraliaPeter MacCallum Cancer Centre Melbourne VIC AustraliaAbstract We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin‐fixed paraffin‐embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non‐cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD‐L1, and PD‐1 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24‐immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, P < .001 and worse survival for LSCC, P = .038). OTSCC exhibited concordant gene and immunohistochemical (IHC) features characterized by a TH‐2 biased, proinflammatory profile with upregulated B cell and neutrophil gene activity and increased CD4, FOXP3, and PD‐L1 expression (P < .001 for all by IHC). Compared to less advanced disease, nodal involvement and recurrent OTSCC did not induce a different immune response although recurrent disease was characterized by significantly higher PD‐L1 expression (P = .004 by SP263, P = .013 by 22C3, P = .004 for gene expression). Identification of a gene signature associated with different prognostic effects in other cancers highlights common pathways of immune dysregulation that are impacted by the tumor origin. The significant immunosuppressive signaling in OTSCC indicates primary failure of immune system to control carcinogenesis emphasizing the need for early, combination therapeutic approaches.https://doi.org/10.1002/cam4.3106FOXP3Immune signatureoral tongue squamous cell carcinomaPD‐L1 |
| spellingShingle | Katie Meehan Connull Leslie Michaela Lucas Angela Jacques Bob Mirzai James Lim Max Bulsara Yasir Khan Nicholas C. Wong Benjamin Solomon Chady Sader Peter Friedland Gisela Mir Arnau Timothy Semple Annette M. Lim Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease Cancer Medicine FOXP3 Immune signature oral tongue squamous cell carcinoma PD‐L1 |
| title | Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease |
| title_full | Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease |
| title_fullStr | Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease |
| title_full_unstemmed | Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease |
| title_short | Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease |
| title_sort | characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease |
| topic | FOXP3 Immune signature oral tongue squamous cell carcinoma PD‐L1 |
| url | https://doi.org/10.1002/cam4.3106 |
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