CD28-CD57+ T cells from head and neck cancer patients produce high levels of cytotoxic granules and type II interferon but are not senescent

Brendan L C Kinney; Brianna Brammer; Vikash Kansal; Connor J Parrish; Haydn T Kissick; Yuan Liu; Nabil F Saba; Zachary S Buchwald; Mark W El-Deiry; Mihir R Patel; Brian J Boyce; Azeem S Kaka; Jennifer H Gross; H Michael Baddour; Amy Y Chen; Nicole C Schmitt

doi:10.1080/2162402X.2024.2367777

CD28-CD57+ T cells from head and neck cancer patients produce high levels of cytotoxic granules and type II interferon but are not senescent

Oncoimmunology. 2024 Jun 14;13(1):2367777. doi: 10.1080/2162402X.2024.2367777. eCollection 2024.

Authors

Brendan L C Kinney^{1

2}, Brianna Brammer^{1

2}, Vikash Kansal^{1

2}, Connor J Parrish³, Haydn T Kissick^{2

4

5}, Yuan Liu^{2

6}, Nabil F Saba^{2

7}, Zachary S Buchwald⁸, Mark W El-Deiry^{1

2}, Mihir R Patel^{1

2}, Brian J Boyce^{1

2}, Azeem S Kaka^{1

2}, Jennifer H Gross^{1

2}, H Michael Baddour^{1

2}, Amy Y Chen^{1

2}, Nicole C Schmitt^{1

2}

Affiliations

¹ Department of Otolaryngology - Head and Neck Surgery, Emory University, Atlanta, GA, USA.
² Winship Cancer Institute, Emory University, Atlanta, GA, USA.
³ School of Medicine, St. Louis University School of Medicine, St. Louis, MO, USA.
⁴ Department of Urology, Emory University, Atlanta, GA, USA.
⁵ Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
⁶ Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
⁷ Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
⁸ Department of Radiation Oncology, Emory University, Atlanta, GA, USA.

Abstract

T lymphocytes expressing CD57 and lacking costimulatory receptors CD27/CD28 have been reported to accumulate with aging, chronic infection, and cancer. These cells are described as senescent, with inability to proliferate but enhanced cytolytic and cytokine-producing capacity. However, robust functional studies on these cells taken directly from cancer patients are lacking. We isolated these T cells and their CD27/28+ counterparts from blood and tumor samples of 50 patients with previously untreated head and neck cancer. Functional studies confirmed that these cells have enhanced ability to degranulate and produce IFN-γ. They also retain the ability to proliferate, thus are not senescent. These data suggest that CD27/28-CD57+ CD8+ T cells are a subset of highly differentiated, CD45RA+ effector memory (T_EMRA) cells with retained proliferative capacity. Patients with > 34% of these cells among CD8+ T cells in the blood had a higher rate of locoregional disease relapse, suggesting these cells may have prognostic significance.

Keywords: CD28; CD57; KLRG1; TEMRA cells; cellular senescence; costimulation; head and neck cancer.

MeSH terms

Adult
Aged
Aged, 80 and over
CD28 Antigens* / metabolism
CD57 Antigens* / metabolism
CD8-Positive T-Lymphocytes* / immunology
Cell Proliferation
Cellular Senescence / immunology
Female
Head and Neck Neoplasms* / immunology
Head and Neck Neoplasms* / pathology
Humans
Interferon-gamma* / metabolism
Male
Middle Aged

Substances

CD28 Antigens
CD57 Antigens
Interferon-gamma

Grants and funding

This work was funded by Winship Cancer Institute, the Department of Otolaryngology – Head and Neck Surgery at Emory University School of Medicine, and the Emory Woodruff Health Sciences Center for Health in Aging. Research reported in this publication was supported in part by the Winship Cancer Tissue and Pathology Resource, Emory Pediatrics/ Winship Flow Cytometry Core, Emory Integrated Genomics Core, and NIH/NCI under award number [P30CA138292].