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Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture. Transl Oncol 2024 Apr;42:101899

Date

02/07/2024

Pubmed ID

38320395

Pubmed Central ID

PMC10851216

DOI

10.1016/j.tranon.2024.101899

Scopus ID

2-s2.0-85184507548 (requires institutional sign-in at Scopus site)

Abstract

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.

Author List

Zenga J, Awan M, Frei A, Foeckler J, Kuehn R, Espinosa OV, Bruening J, Massey B, Wong S, Shreenivas A, Shukla M, Kasprzak J, Sun Y, Shaheduzzaman M, Chen F, Kearl T, Himburg HA

Authors

Musaddiq J. Awan MD Assistant Professor in the Radiation Oncology department at Medical College of Wisconsin
Heather A. Himburg PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin
Tyce J. Kearl MD, PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Monica E. Shukla MD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin
Yunguang Sun MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin
Joseph Zenga MD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin