Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324000251 |
| _version_ | 1797322402850406400 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Joseph Zenga |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T05:13:48Z |
| format | Article |
| id | doaj.art-17155342d9804d488549332997db6abf |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-08T05:13:48Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-17155342d9804d488549332997db6abf2024-02-07T04:44:27ZengElsevierTranslational Oncology1936-52332024-04-0142101899Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-cultureJoseph Zenga0Musaddiq Awan1Anne Frei2Jamie Foeckler3Rachel Kuehn4Oscar Villareal Espinosa5Jennifer Bruening6Becky Massey7Stuart Wong8Aditya Shreenivas9Monica Shukla10Julia Kasprzak11Yunguang Sun12Md Shaheduzzaman13Fanghong Chen14Tyce Kearl15Heather A. Himburg16Cancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCancer Center, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States; Corresponding author at: Radiation Oncology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, United States.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.http://www.sciencedirect.com/science/article/pii/S1936523324000251Head and neck cancerT cellTumor-infiltrating lymphocyteImmunotherapy |
| spellingShingle | 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 Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture Translational Oncology Head and neck cancer T cell Tumor-infiltrating lymphocyte Immunotherapy |
| title | Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture |
| title_full | Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture |
| title_fullStr | Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture |
| title_full_unstemmed | Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture |
| title_short | Tumor-specific T cells in head and neck cancer have rescuable functionality and can be identified through single-cell co-culture |
| title_sort | tumor specific t cells in head and neck cancer have rescuable functionality and can be identified through single cell co culture |
| topic | Head and neck cancer T cell Tumor-infiltrating lymphocyte Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324000251 |
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