Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment

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 spat...

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Main Authors: Linda Chen, Nancy Lee, Reith Sarkar, Nora Katabi, Yanyun Li, Luc Morris, Richard Wong, Eric Sherman, Jorge S. Reis-Filho, Travis Hollmann, Nadeem Riaz
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2023.2230666
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author Linda Chen
Nancy Lee
Reith Sarkar
Nora Katabi
Yanyun Li
Luc Morris
Richard Wong
Eric Sherman
Jorge S. Reis-Filho
Travis Hollmann
Nadeem Riaz
author_facet Linda Chen
Nancy Lee
Reith Sarkar
Nora Katabi
Yanyun Li
Luc Morris
Richard Wong
Eric Sherman
Jorge S. Reis-Filho
Travis Hollmann
Nadeem Riaz
author_sort Linda Chen
collection DOAJ
description 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.
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spelling doaj-art-0dadcc7e8ad74a70b735fcf5d19e09892024-12-27T17:34:38ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2230666Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironmentLinda Chen0Nancy Lee1Reith Sarkar2Nora Katabi3Yanyun Li4Luc Morris5Richard Wong6Eric Sherman7Jorge S. Reis-Filho8Travis Hollmann9Nadeem Riaz10Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesHuman 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.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2230666TCF1+ T-cellHPVhead and neck cancertumor immune microenvironmentrecurrentchemoradiation
spellingShingle Linda Chen
Nancy Lee
Reith Sarkar
Nora Katabi
Yanyun Li
Luc Morris
Richard Wong
Eric Sherman
Jorge S. Reis-Filho
Travis Hollmann
Nadeem Riaz
Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment
OncoImmunology
TCF1+ T-cell
HPV
head and neck cancer
tumor immune microenvironment
recurrent
chemoradiation
title Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment
title_full Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment
title_fullStr Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment
title_full_unstemmed Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment
title_short Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment
title_sort stem cell like t cell depletion in the recurrent head and neck cancer immune microenvironment
topic TCF1+ T-cell
HPV
head and neck cancer
tumor immune microenvironment
recurrent
chemoradiation
url https://www.tandfonline.com/doi/10.1080/2162402X.2023.2230666
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