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.
Skewed T cell differentiation in indolent non-Hodgkin's lymphoma patients reversed by ex-vivo T cell culture with {gamma}c-cytokines / A. Anichini, R. Mortarini, L. Romagnoli, P. Baldassari, A. Cabras, C. Carlo-Stella, A.M. Gianni, M. Di Nicola. - In: BLOOD. - ISSN 0006-4971. - 107:2(2006), pp. 602-609. [10.1182/blood-2005-06-2234]
Skewed T cell differentiation in indolent non-Hodgkin's lymphoma patients reversed by ex-vivo T cell culture with {gamma}c-cytokines
C. Carlo-Stella;A.M. GianniPenultimo
;
2006
Abstract
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.Pubblicazioni consigliate
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