Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with γc cytokines

• Published in: Blood 2006-01, Vol.107 (2), p.602-609
• Main Authors: Anichini, Andrea, Mortarini, Roberta, Romagnoli, Luca, Baldassari, Paola, Cabras, Antonello, Carlo-Stella, Carmelo, Gianni, Alessandro M., Di Nicola, Massimo
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Hematologic and hematopoietic diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-06-2234

The unfavorable clinical evolution in indolent non-Hodgkin lymphomas suggests defective control of neoplastic growth by the immune system. To address this issue, we evaluated phenotype, function, and maturation profile of CD4+ and CD8+ T cells from peripheral-blood, lymph nodes, or bone marrow of patients with B-cell non-Hodgkin lymphoma (NHL) at diagnosis. T cells from these patients frequently showed an activated but apoptosis-prone phenotype with low frequency of tumor-reactive T cells showing a TH2/Tc2 functional profile in the response to autologous tumor. In peripheral blood or in lymph nodes and bone marrow, and, in comparison to healthy donors, patients' T cells showed a skewed differentiation toward Tnaive and Tcentral memory stages, with low expression of granzyme B and perforin. T-cell culture with autologous tumor in the presence of IL-2, IL-15, and autologous bone marrow–derived cells led to massive T-cell expansion and to differentiation of cytotoxic factor+ CD8+ T cells releasing IFN-γ and killing autologous B-cell tumor in an HLA-class I–restricted fashion. These results suggest impaired T-cell differentiation to effector stage in patients with B-cell NHL, but indicate that T-cell responsiveness to γc cytokines is retained, thus allowing to promote generation of antitumor T cells for immune intervention.