Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture

Autor: Joseph Zenga, Musaddiq Awan, Anne Frei, Jamie Foeckler, Rachel Kuehn, Oscar Villareal Espinosa, Jennifer Bruening, Becky Massey, Stuart Wong, Aditya Shreenivas, Monica Shukla, Julia Kasprzak, Yunguang Sun, Md Shaheduzzaman, Fanghong Chen, Tyce Kearl, Heather A. Himburg
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Translational Oncology, Vol 42, Iss , Pp 101899- (2024)
Druh dokumentu: article
ISSN: 1936-5233
DOI: 10.1016/j.tranon.2024.101899
Popis: Background: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains a treatment-resistance disease with limited response to immunotherapy. While T cells in HNSCC are known to display phenotypic dysfunction, whether they retain rescuable functional capacity and tumor-killing capability remains unclear. Methods: To investigate the functionality and tumor-specificity of tumor-infiltrating lymphocytes (TILs) across HNSCCs, malignant cell lines and TILs were derived from 31 HPV-negative HNSCCs at the time of standard surgical resection. T cell functional capacity was evaluated through ex vivo expansion, immunophenotyping, and IsoLight single-cell proteomics. Tumor-specificity was investigated through both bulk and single-cell tumor-TIL co-culture. Results: TILs could be successfully generated from 24 patients (77%), including both previously untreated and radiation recurrent HNSCCs. We demonstrate that across HNSCCs, TILs express multiple exhaustion markers but maintain a predominantly effector memory phenotype. After ex vivo expansion, TILs retain immunogenic functionality even from radiation-resistant, exhausted, and T cell-depleted disease. We further demonstrate tumor-specificity of T cells across HNSCC patients through patient-matched malignant cell-T cell co-culture. Finally, we use optofluidic technology to establish an autologous single tumor cell-single T cell co-culture platform for HNSCC. Cells derived from three HNSCC patients underwent single-cell co-culture which enabled identification and visualization of individual tumor-killing TILs in real-time in all patients. Conclusions: These studies show that cancer-specific T cells exist across HNSCC patients with rescuable immunogenicity and can be identified on a single-cell level. These data lay the foundation for development of patient-specific T cell immunotherapies in HNSCC.
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