Dichotomous and stable gamma delta T-cell number and function in healthy individuals

• DOI: 10.1136/jitc-2020-002274
• Publication Date: 2021-05-19T17:36:03Z
• Authors: Lingling Ou; Huaishan Wang; Qin Liu; Jie Zhang; Hezhe Lu; Liangping Luo; Changzheng Shi; Shaoqiang Lin; Liyun Dong; Yeye Guo; Lili Huang; Jinjin Zhu; Xiangfan Yin; Alexander C Huang; Giorgos Karakousis; Lynn Schuchter; Ravi Amaravadi; Cathy Zheng; Yi Fan; Wei Guo; Xiaowei Xu
• Keywords: Adult; Cytotoxicity, Immunologic; Male; 0301 basic medicine; Skin Neoplasms; Lymphocyte Activation; Immunophenotyping; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Humans; Lymphocyte Count; Intraepithelial Lymphocytes; Melanoma; RC254-282; Cell Proliferation; Clinical/Translational Cancer Immunotherapy; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Middle Aged; Coculture Techniques; Healthy Volunteers; 3. Good health; Phenotype; Female; Immunologic Memory; Biomarkers

Background Gamma-delta (γδ) T lymphocytes are primed to potently respond pathogens and transformed cells by recognizing a broad range of antigens. However, adoptive immunotherapy with γδT has exhibited mixed treatment responses. Better understanding cell biology stratifying healthy donors for allogeneic therapy is clinically needed fully realize the therapeutic potential cells. Methods We examine 98 blood samples from measure their expansion capacity after zoledronate stimulation, test migration cytotoxic effector function expanded in 2D culture, 3D tumor spheroid patient-derived melanoma organoid assays. Results find that independent methods, gender, age HLA type. Basal levels Peripheral mononuclear (PBMC) correlate well expansion, vitro. Circulating lower expression PD-1, CTLA-4, Eomes, T-bet CD69, or higher IFN-γ production expand better. central memory phenotypes significantly more abundant good expanders. A cut-off level 0.82% PBMC stratifies versus poor sensitivity 97.78%, specificity 90.48% area under curve 0.968 individual. Donors Vδ2 Index Score have greater anti-tumor functions including migratory cytotoxicity. Conclusions Our results demonstrate interindividual circulating donors. Examination may be used select participate γδT-based immunotherapies.