Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment Journal Article
| Authors: | Chen, L.; Lee, N.; Sarkar, R.; Katabi, N.; Li, Y.; Morris, L.; Wong, R.; Sherman, E.; Reis-Filho, J. S.; Hollmann, T.; Riaz, N. |
| Article Title: | Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment |
| Abstract: | Human papilloma virus (HPV)-related oncogenesis in head and neck cancer establishes a local microenvironment rich with immune cells, however the composition of the microenvironment in recurrent disease following definitive treatment is poorly understood. Here, we investigate the composition and spatial relationships between tumor and immune cells in recurrent head and neck cancer following curative intent chemoradiotherapy. Multiplexed immunofluorescence with 12 unique markers, through two multiplex immunofluorescent panels, was performed to evaluate 27 tumor samples including 18 pre-treatment primary and 9 paired recurrent tumors. Tumor and immune cell populations were phenotyped and quantified using a previously validated semi-automated digital pathology platform for cell segmentation. Spatial analysis was conducted by evaluating immune cells within the tumor, peri-tumoral stroma, and distant stroma. Initial tumors in patients with subsequent recurrence were found to be enriched in tumor associated macrophages and displayed an immune excluded spatial distribution. Recurrent tumors after chemoradiation were hypo-inflamed, with a statistically significant reduction in the recently identified stem-like TCF1+ CD8 T-cells, which normally function to maintain HPV-specific immune responses in the setting of chronic antigen exposure. Our findings indicate that the tumor microenvironment of recurrent HPV-related head and neck cancers displays a reduction in stem-like T cells, consistent with an immune microenvironment with a reduced ability to mount T-cell-driven anti-tumor immune responses. © 2023 The Author(s). Published with license by Taylor & Francis Group, LLC. |
| Keywords: | immunohistochemistry; clinical article; human tissue; protein expression; overall survival; histopathology; cancer recurrence; cisplatin; disease free survival; cancer staging; follow up; cd8 antigen; cd8+ t lymphocyte; t lymphocyte; tumor associated leukocyte; cd8-positive t-lymphocytes; cancer immunotherapy; gene expression; image analysis; tumor volume; immunofluorescence; cell population; histology; distant metastasis; carcinogenesis; stem cell; in situ hybridization; head and neck cancer; tumor recurrence; stroma; stem cells; cd4 antigen; tissue microarray; tumor growth; t cell depletion; macrophage; disease specific survival; chemoradiation; immunocompetent cell; fluorescence imaging; chemoradiotherapy; wart virus; papillomavirus infections; recurrent; head and neck squamous cell carcinoma; tumor microenvironment; complication; tumor-associated macrophage; papillomavirus infection; spatial analysis; hpv; environmental health; lymphatic system tumor; cancer prognosis; humans; human; article; tumor immune microenvironment; human papillomavirus viruses; tcf1+ t-cell |
| Journal Title: | OncoImmunology |
| Volume: | 12 |
| ISSN: | 2162-4011 |
| Publisher: | Landes Bioscience |
| Date Published: | 2023-01-01 |
| Start Page: | 2230666 |
| Language: | English |
| DOI: | 10.1080/2162402x.2023.2230666 |
| PUBMED: | 37435097 |
| PROVIDER: | scopus |
| PMCID: | PMC10332189 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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