Prognostic impact of intra- and peritumoral immune cell subpopulations in head and neck squamous cell carcinomas – comprehensive analysis of the TCGA-HNSC cohort and immunohistochemical validation…

By M. Knebel, S. Körner, J. Kühn, S. Wemmert, L. Brust, S. Smola, M. Wagner, R. Bohle, L. Morris, Abhinav Pandey and 2 more. Frontiers in Immunology, 2023

13 citations recorded by the source corpus.

Background Due to the expanding role of immune checkpoint inhibition in the treatment of head and neck squamous cell carcinoma, understanding immunological processes in the tumor microevironment (TME) has strong translational importance. Though analytical methods for a comprehensive analysis of the immunological TME have constantly improved and expanded over the past years the prognostic relevance of immune cell composition in head and neck cancer TME largely remains ambiguous with most studies focusing on one or a small subset of immune cells. Methods The overall survival (OS) of the TCGA-HNSC patient cohort comprising 513 head and neck cancer patients was correlated with a total of 29 different immune metrics including a wide spectrum of immune cell subpopulations as well as immune checkpoint receptors and cytokines using RNAseq based immune deconvolution analyses. The most significant predictors of survival among these 29 immune metrics were validated on a separate HNSCC patient cohort (n=101) using immunohistochemistry: CD3, CD20+CXCR5, CD4+CXCR5, Foxp3 and CD68. Results Overall immune infiltration irrespective of immune cell composition showed no significant correlation with the patients’ overall survival in the TCGA-HNSC cohort. However, when focusing on different immune cell subpopulations, naïve B cells (p=0.0006), follicular T-helper cells (p<0.0001), macrophages (p=0.0042), regulatory T cells (p=0.0306), lymphocytes (p=0.0001), and cytotoxic T cells (p=0.0242) were identified as highly significant predictors of improved patient survival. Using immunohistochemical detection of these immune cells in a second independent validation cohort of 101 HNSCC patients, we confirmed the prognostic relevance of follicular T helper cells, cytotoxic T cells and lymphocytes. In multivariable analysis, HPV negativity and advanced UICC stages were identified as additional prognostic biomarkers associated with poor outcome. Conclusion Our study highlights the prognostic relevance of the immunological tumor environment in head and neck cancer and demonstrates that a more detailed analysis of immune cell composition and immune cell subtypes is necessary to accurately prognosticate. We observed the highest prognostic relevance for lymphocytes, cytotoxic T cells, and follicular T helper cells, suggesting further investigations focusing on these specific immune cell subpopulations not only as predictors of patient prognosis but also as promising targets of new immunotherapeutic strategies.

Subfields: Immunology, Oncology, Otorhinolaryngology

View Paper: https://doi.org/10.3389/fimmu.2023.1172768

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Citations in the corpus

Small Extracellular Vesicle Cargoes Associated with Lymph Node Metastasis in Head and Neck Cancer (2026, unknown): “To connect our proteomics and tumor findings with potential prognostic biomarkers based on SEVs, we analyzed gene expression profiles in a cohort of 499 HNSCC patients with RNA-Seq data from the publicly available TCGA database (31, 32).”
Unraveling the Role of Tumor-Infiltrating Immune Cells in Head and Neck Squamous Cell Carcinoma: Implications for Antitumor Immune Responses and Immunotherapy (2025, unknown): “Furthermore, the presence of certain mutations, such as the tumor protein 53 (TP53) mutation, can influence the phenotype and abundance of tumor-infiltrating immune cells [9].”
The Single-Cell Landscape of Peripheral and Tumor-infiltrating Immune Cells in HPV- HNSCC (2025, unknown): “45 To further investigate the role of cytotoxic immune cells in HPV-negative HNSCC, we conducted a focused multiplexed immunofluorescence (Multi-IF) experiment using the Phenocycler-Fusion 2.0 (Akoya Biosciences) to profile specific cytotoxic immune cell states within the tumor microenvironment.”
Intratumoral and peritumoral radiomics of MRIs predicts pathologic complete response to neoadjuvant chemoimmunotherapy in patients with head and neck squamous cell carcinoma (2024, unknown): “40 Peritumoral and intra-tumoral areas may have a different composition of cell types and be valued differently in immunotherapy.”
Comprehensive Transcriptome Analysis Reveals the Distinct Gene Expression Patterns of Tumor Microenvironment in HPV-Associated and HPV-Non Associated Tonsillar Squamous Cell Carcinoma (2023, methodology): “The following supporting information can be downloaded at https:// www.mdpi.com/article/10.3390/cancers15235548/s1: Table S1: UniGene, GenBank, Symbol, and description of Genes; Table S2: PCR primers used for HPV genotyping and oncogene integration detection.”