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Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%–20% of patients and underpinnings of resistance remain undefined. METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogeni...

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Autores principales: Zhou, Liye, Zeng, Zexian, Egloff, Ann Marie, Zhang, Fan, Guo, Fei, Campbell, Katie M, Du, Peter, Fu, Jingxin, Zolkind, Paul, Ma, Xiaojing, Zhang, Zhe, Zhang, Yi, Wang, Xiaoqing, Gu, Shengqing, Riley, Rachel, Nakahori, Yasutaka, Keegan, Joshua, Haddad, Robert, Schoenfeld, Jonathan D, Griffith, Obi, Manguso, Robert T, Lederer, James A, Liu, X Shirley, Uppaluri, Ravindra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772459/
https://www.ncbi.nlm.nih.gov/pubmed/35058328
http://dx.doi.org/10.1136/jitc-2021-004034
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author Zhou, Liye
Zeng, Zexian
Egloff, Ann Marie
Zhang, Fan
Guo, Fei
Campbell, Katie M
Du, Peter
Fu, Jingxin
Zolkind, Paul
Ma, Xiaojing
Zhang, Zhe
Zhang, Yi
Wang, Xiaoqing
Gu, Shengqing
Riley, Rachel
Nakahori, Yasutaka
Keegan, Joshua
Haddad, Robert
Schoenfeld, Jonathan D
Griffith, Obi
Manguso, Robert T
Lederer, James A
Liu, X Shirley
Uppaluri, Ravindra
author_facet Zhou, Liye
Zeng, Zexian
Egloff, Ann Marie
Zhang, Fan
Guo, Fei
Campbell, Katie M
Du, Peter
Fu, Jingxin
Zolkind, Paul
Ma, Xiaojing
Zhang, Zhe
Zhang, Yi
Wang, Xiaoqing
Gu, Shengqing
Riley, Rachel
Nakahori, Yasutaka
Keegan, Joshua
Haddad, Robert
Schoenfeld, Jonathan D
Griffith, Obi
Manguso, Robert T
Lederer, James A
Liu, X Shirley
Uppaluri, Ravindra
author_sort Zhou, Liye
collection PubMed
description BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%–20% of patients and underpinnings of resistance remain undefined. METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models. RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. Immunoprofiling showed distinct baseline tumor microenvironments of MOC1 and MOC1esc1, as well as the remodeling of immune compartments on ICB in MOC1esc1 tumors. Single cell sequencing analysis identified several CD8 +TIL subsets including Tcf7 +Pd1− (naïve/memory-like), Tcf7 +Pd1+ (progenitor), and Tcf7-Pd1+ (differentiated effector). Mapping TCR shared fractions identified that successful anti-PD1 or anti-CTLA4 therapy-induced higher post-treatment T cell lineage transitions. CONCLUSIONS: These data highlight critical aspects of CD8 +TIL heterogeneity and differentiation and suggest facilitation of CD8 +TIL differentiation as a strategy to improve HNSCC ICB response.
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spelling pubmed-87724592022-02-04 Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders Zhou, Liye Zeng, Zexian Egloff, Ann Marie Zhang, Fan Guo, Fei Campbell, Katie M Du, Peter Fu, Jingxin Zolkind, Paul Ma, Xiaojing Zhang, Zhe Zhang, Yi Wang, Xiaoqing Gu, Shengqing Riley, Rachel Nakahori, Yasutaka Keegan, Joshua Haddad, Robert Schoenfeld, Jonathan D Griffith, Obi Manguso, Robert T Lederer, James A Liu, X Shirley Uppaluri, Ravindra J Immunother Cancer Clinical/Translational Cancer Immunotherapy BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%–20% of patients and underpinnings of resistance remain undefined. METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models. RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. Immunoprofiling showed distinct baseline tumor microenvironments of MOC1 and MOC1esc1, as well as the remodeling of immune compartments on ICB in MOC1esc1 tumors. Single cell sequencing analysis identified several CD8 +TIL subsets including Tcf7 +Pd1− (naïve/memory-like), Tcf7 +Pd1+ (progenitor), and Tcf7-Pd1+ (differentiated effector). Mapping TCR shared fractions identified that successful anti-PD1 or anti-CTLA4 therapy-induced higher post-treatment T cell lineage transitions. CONCLUSIONS: These data highlight critical aspects of CD8 +TIL heterogeneity and differentiation and suggest facilitation of CD8 +TIL differentiation as a strategy to improve HNSCC ICB response. BMJ Publishing Group 2022-01-19 /pmc/articles/PMC8772459/ /pubmed/35058328 http://dx.doi.org/10.1136/jitc-2021-004034 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Clinical/Translational Cancer Immunotherapy
Zhou, Liye
Zeng, Zexian
Egloff, Ann Marie
Zhang, Fan
Guo, Fei
Campbell, Katie M
Du, Peter
Fu, Jingxin
Zolkind, Paul
Ma, Xiaojing
Zhang, Zhe
Zhang, Yi
Wang, Xiaoqing
Gu, Shengqing
Riley, Rachel
Nakahori, Yasutaka
Keegan, Joshua
Haddad, Robert
Schoenfeld, Jonathan D
Griffith, Obi
Manguso, Robert T
Lederer, James A
Liu, X Shirley
Uppaluri, Ravindra
Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders
title Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders
title_full Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders
title_fullStr Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders
title_full_unstemmed Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders
title_short Checkpoint blockade-induced CD8+ T cell differentiation in head and neck cancer responders
title_sort checkpoint blockade-induced cd8+ t cell differentiation in head and neck cancer responders
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772459/
https://www.ncbi.nlm.nih.gov/pubmed/35058328
http://dx.doi.org/10.1136/jitc-2021-004034
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