Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can be expanded in vitro

• Published in: Blood 1997-05, Vol.89 (10), p.3806-3816
• Main Authors: SCHULTZE, J. L, SEAMON, M. J, MICHALAK, S, GRIBBEN, J. G, NADLER, L. M
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - immunology; B-Lymphocytes - pathology; Biological and medical sciences; Cells, Cultured; Chromosomes, Human, Pair 14 - ultrastructure; Chromosomes, Human, Pair 18 - ultrastructure; Cytotoxicity, Immunologic; Hematologic and hematopoietic diseases; Humans; Interferon-gamma - pharmacology; Interleukin-12 - pharmacology; Interleukin-2 - pharmacology; Interleukin-4 - pharmacology; Interleukin-7 - pharmacology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation - drug effects; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Lymphoma, Follicular - pathology; Medical sciences; Neoplastic Stem Cells - immunology; Neoplastic Stem Cells - pathology; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - pathology; Translocation, Genetic
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V89.10.3806

Follicular lymphomas (FLs) rarely induce clinically significant T-cell-mediated responses. We showed that freshly isolated tumor infiltrating T cells (T-TILs) lack tumor-specific cytotoxicity. Stimulation of these T cells with FL cells in the presence of interleukin-2 (IL-2) and/or costimulation via CD28 does not lead to T-cell activation and expansion. In contrast, when stimulated with FL cells preactivated via CD40, autologous T-TILs can be expanded by the addition of exogenous IL-2. These T cells can be further expanded in vitro by the addition of exogenous IL-4, IL-7, or interferon-gamma, but not IL-12. Once activated, these T cells showed FL-directed cytotoxicity in four of five patients tested. We concluded that autologous cytotoxic anti-FL-specific T cells exist, but can only be detected in vitro under optimized conditions for T-cell stimulation and expansion. This suggests that their frequency in vivo is either very low or that the microenvironment does not provide the necessary signals to activate these T cells. This model system allows dissection of the requisite conditions for activation and expansion of lymphoma-directed cytotoxicity and may permit expansion of previously activated cytotoxic T cells for adoptive transfer.