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Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease

ABSTRACT: Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease

PROVIDER: PRJNA626590 | ENA |

REPOSITORIES: ENA

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Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease

Project description: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. 110 FFPE 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 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<0.001 and worse survival for LSCC, p=0.038). OTSCC exhibited concordant gene and IHC features characterized by a TH-2 biased, pro-inflammatory profile with upregulated B cell and neutrophil gene activity and increased CD4, FOXP3 and PD-L1 expression (p<0.001 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=0.004 by SP263, p=0.013 by 22C3, p=0.004 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.

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A minimal DNA 5-methylcytosine signature of oral tongue squamous cell carcinoma [methylation]

Project description:Oral tongue squamous cell carcinomas (OTSCC) are a homogenous group of aggressive tumors in the head and neck region, with a rising incidence among younger population. The role of altered DNA methylation in OTSCC and its link with clinical parameters has not been fully assessed yet. We performed genome-wide methylation analysis of oral tongue primary tumors (n = 52) using 485, 512 probes and correlated altered methylation with differences in gene expression. We used an ensemble machine-learning algorithm to identify differentially methylated probes and regions predictive of survival, risk habits, nodal status, tumor stage, and HPV infection followed by validation using data from the cancer genome atlas (TCGA) project on oral tongue (n = 24) and tumors from all subsites of head and neck region (n = 50).

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