1. Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue
- Author
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Joaquin J. Garcia, Kyriakos Chatzopoulos, Andrea R. Collins, Alessandra C. Schmitt, Sotiris Sotiriou, Michael L. Hinni, Xianfeng Chen, Matthew A. Zarka, Khashayarsha Khazaie, Samir H. Patel, Panagiotis Kartsidis, and Colleen Ramsower
- Subjects
Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Cell ,chemical and pharmacologic phenomena ,Immunophenotyping ,Pathology and Forensic Medicine ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,TIGIT ,Tongue ,Gene expression ,Tumor Microenvironment ,medicine ,Humans ,Aged ,Original Paper ,Tumor microenvironment ,Squamous Cell Carcinoma of Head and Neck ,Tumor-infiltrating lymphocytes ,business.industry ,Gene Expression Profiling ,FOXP3 ,Middle Aged ,Tongue Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,Transcriptome ,business - Abstract
The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R(2) = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.
- Published
- 2020