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Blood, 15 January 2006, Vol. 107, No. 2, pp. 602-609.
Prepublished online as a Blood First Edition Paper on September 8, 2005; DOI 10.1182/blood-2005-06-2234.
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Submitted June 3, 2005
Accepted August 11, 2005
Skewed T cell differentiation in indolent non-Hodgkin's lymphoma patients reversed by ex-vivo T cell culture with  c-cytokines
Andrea Anichini, Roberta Mortarini, Luca Romagnoli, Paola Baldassari, Antonello Cabras, Carmelo Carlo-Stella, Alessandro M Gianni*, and Massimo Di Nicola
Human Tumor Immunobiology Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
"Cristina Gandini" Bone Marrow Transplantation Unit, Department of Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
"Cristina Gandini" Bone Marrow Transplantation Unit, Department of Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; Chair of Medical Oncology, University of Milan, Milan, Italy
* Corresponding author; email: alessandro.gianni{at}unimi.it.
The unfavourable clinical evolution in indolent non-Hodgkin's 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 B cell NHL patients 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 towards 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- and killing autologous B cell tumor in an HLA-Class I-restricted fashion. These results suggest impaired T cell differentiation to effector stage in B cell NHL patients, but indicate that T cell responsiveness to c cytokines is retained, thus allowing to promote generation of anti-tumor T cells for immune intervention.
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