Immune cell topography of head and neck cancer

BackgroundApproximately 50% of head and neck squamous cell carcinomas (HNSCC) recur after treatment with curative intent. Immune checkpoint inhibitors are treatment options for recurrent/metastatic HNSCC; however, less than 20% of patients respond. To increase this response rate, it is fundamental t...

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Published in:Journal for immunotherapy of cancer Vol. 12; no. 7; p. e009550
Main Authors: Muijlwijk, Tara, Nijenhuis, Dennis N L M, Ganzevles, Sonja H, Ekhlas, Fatima, Ballesteros-Merino, Carmen, Peferoen, Laura A N, Bloemena, Elisabeth, Fox, Bernard A, Poell, Jos B, Leemans, C René, Brakenhoff, Ruud H, van de Ven, Rieneke
Format: Journal Article
Language:English
Published: England BMJ Publishing Group Ltd 24.07.2024
BMJ Publishing Group LTD
BMJ Publishing Group
Subjects:
Aged
Antigens
B cell
Basic Tumor Immunology
Cells
Cytotoxicity
Female
Head & neck cancer
Head and Neck Cancer
Head and Neck Neoplasms - immunology
Head and Neck Neoplasms - pathology
Human papillomavirus
Humans
Lymphocytes
Lymphocytes, Tumor-Infiltrating - immunology
Lymphocytes, Tumor-Infiltrating - metabolism
Macrophage
Macrophages - immunology
Macrophages - metabolism
Male
Medical prognosis
Middle Aged
Neighborhoods
Original Research
Proteins
Squamous cell carcinoma
Squamous Cell Carcinoma of Head and Neck - immunology
Squamous Cell Carcinoma of Head and Neck - pathology
T cell
Topography
Tumor Microenvironment - immunology
Tumor microenvironment - TME
Tumors
Head and Neck Cancer
B cell
Tumor microenvironment - TME
T cell
Macrophage
ISSN:2051-1426, 2051-1426
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Summary:BackgroundApproximately 50% of head and neck squamous cell carcinomas (HNSCC) recur after treatment with curative intent. Immune checkpoint inhibitors are treatment options for recurrent/metastatic HNSCC; however, less than 20% of patients respond. To increase this response rate, it is fundamental to increase our understanding of the spatial tumor immune microenvironment (TIME).MethodsIn total, 53 HNSCC specimens were included. Using a seven-color multiplex immunohistochemistry panel we identified tumor cells, CD163+macrophages, B cells, CD8+T cells, CD4+T helper cells and regulatory T cells (Tregs) in treatment-naive surgical resection specimens (n=29) and biopsies (n=18). To further characterize tumor-infiltrating CD8+T cells, we stained surgical resection specimens (n=12) with a five-color tumor-resident panel including CD103, Ki67, CD8 and pan-cytokeratin. Secretome analysis was performed on matched tumor suspensions (n=11) to measure protein levels.ResultsBased on CD8+T cell infiltrates, we identified four different immunotypes: fully infiltrated, stroma-restricted, immune-excluded, and immune-desert. We found higher cytokine levels in fully infiltrated tumors compared with other immunotypes. While the highest immune infiltrates were observed in the invasive margin for all immune cells, CD163+macrophages and Tregs had the highest tendency to infiltrate the tumor center. Within the tumor center, especially B cells stayed at the tumor stroma, whereas CD163+macrophages, followed by T cells, were more often localized within tumor fields. Also, B cells were found further away from other cells and often formed aggregates while T cells and CD163+macrophages tended to be more closely located to each other. Across resection specimens from various anatomical sites within the head and neck, oral cavity tumors exhibited the highest densities of Tregs. Moreover, the distance from B cells and T cells to tumor cells was shortest in oral cavity squamous cell carcinoma (OCSCC), suggesting more interaction between lymphocytes and tumor cells. Also, the fraction of T cells within 10 µm of CD163+macrophages was lowest in OCSCC, indicating fewer myeloid/T-cell suppressive interactions in OCSCC.ConclusionsWe comprehensively described the TIME of HNSCC using a unique data set of resection specimens. We discovered that the composition, as well as the relative localization of immune cells in the TIME, differed in distinct anatomical sites of the head and neck.
Bibliography:Original research
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Supplement: Additional supplemental material is published online only. To view, please visit the journal online (https://doi.org/10.1136/jitc-2024-009550).
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
None declared.
DNLMN and SHG contributed equally.
ISSN:2051-1426
2051-1426
DOI:10.1136/jitc-2024-009550