Abstract
9589 This study was aimed at investigating the development of T cell-mediated immune response in B cell tumor patients and at defining the optimal conditions for developing adoptive immunotherapy protocols. The following assessments were carried out utilizing T cells isolated from involved lymph-nodes (LN), peripheral blood or bone marrow of patients with indolent NHL (40 follicular, 32 CLL, 8 MCL): 1. distribution of TCRBV repertoire; 2. analysis of the activation profile; 3. analysis of the differentiation phenotype along the naïve to effector and memory stages by expression of CD45RA, CCR7 and cytolytic factors perforin and granzyme B. The analysis of TCRBV repertoire of CD4+ and CD8+ cells indicated very limited T cell expansions in CD4+ cells in a fraction of patients. This data suggested a reduced effect of neoplastic tissue in shaping the TCRBV repertoire in the LN. Therefore, in most instances, both CD4+ and CD8+ cells were not in a resting condition with high expression of CD69, HLA-DR and CD95 associated to a low expression of CD25 and CD122. Finally, both CD4+ and CD8+ T cells in either periphery, or at tumor site, expressed mainly the early stages of differentiation. The skewed maturation of CD4+ and CD8+ T cells was further confirmed by the low/absent expression of perforin and granzyme B. In contrast, the differentiation phenotype of CD4+ and CD8+ T cells from a panel of 47 healthy donors showed all four T cell maturation stages. T cell culture for 1 to 2 weeks, in the presence of cytokines of the γc family, led to down modulation of CCR7 and expression of perforin and granzyme B in T cells from either peripheral blood and tumor site. Co-culture of T cells isolated from tumor-containing LN with irradiated autologous NHL B cells (n=10) in the presence of IL-2+IL-15 led to an average 45-fold increase of number of CD3+ T-lymphocytes and to activation of tumor-specific T cells as assessed by IFN-γ release and tumor lysis assays. Thus, cytokine-driven functional maturation of tumor-specific T cells from B cell tumor patients could represent an option for reversal of impaired differentiation/activation and for development of adoptive immunotherapy strategies. No significant financial relationships to disclose.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.