Clonal analysis of human tumor infiltrating lymphocytes reactive with autologous tumor cells: different target cell specificities of NK-like and cytotoxic T-cell clones |
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| Authors: | H Rabinowich Z Steiner A Klajman |
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| Institution: | 1. Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada;4. Department of Medicine, School of Medicine and Public Health, University of Wisconsin in Madison, Madison, Wisconsin, USA;6. CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China;7. The Third Affiliated Hospital of Soochow University, The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University Medical College, Suzhou Jiangsu, China;8. Mesoblast Ltd., New York, New York, USA;9. Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland;10. Department of Medicine, University of Toronto, Toronto, Ontario, Canada;1. Laboratory of Hematology–Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands;2. Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands;3. Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, Minnesota, USA;1. Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, South Korea;2. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea;3. Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, South Korea;4. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;5. Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, South Korea;6. Department of Biomedical Science, Chonnam National University Graduate School, Gwangju, South Korea |
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| Abstract: | Lymphocytes, derived from surgically resected lung carcinoid tissue, were stimulated in mixed culture with irradiated autologous tumor cells (MLTC). The autologous MLTC-stimulated lymphocytes were found to have killing activity against both autologous tumor cells and NK-sensitive target cells. The lymphoblasts generated during MLTC were isolated and cloned under limiting dilution conditions in the presence of interleukin 2. The cloned cell lines were analyzed for cell phenotype and tested for cytotoxic activity. Three cloned cell lines, out of 19 tested, were found to be cytotoxic either against NK-sensitive target cells (natural killers) or the autologous tumor cells. Two clones, having OKT8 phenotype, caused no lysis of the autologous tumor cells, though both exerted NK-like activity against K562 cells. Only one clone with OKT4 phenotype showed specific cytotoxic activity against the autologous tumor, but no NK-like activity against a panel of tumor target cells. These results suggest the coexistence of two types of antitumor cytotoxic lymphocytes at the tumor site: precursors of NK-like cells and specific cytotoxic T cells. Target cell specificity provided a means of distinguishing between the two types. |
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