Selective responsiveness to common gamma chain cytokines in peripheral blood-derived cytotoxic T lymphocytes induced by Melan-A/MART-127–35targeted active specific immunotherapy
✍ Scribed by Urs von Holzen; Michel Adamina; Martin Bolli; Walter P. Weber; Paul Zajac; Celia Groeper; Anca Reschner; Chantal Feder; Reto Schumacher; Walter Marti; Daniel Oertli; Michael Heberer; Giulio C. Spagnoli
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- French
- Weight
- 392 KB
- Volume
- 115
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
We have comparatively evaluated the proliferative response of CTL induced in metastatic melanoma patients upon immunization against Melan‐A/MART‐1~27–35~ tumor associated antigen (TAA) to IL‐2, IL‐7 or IL‐15 cytokines, sharing a receptor common γ‐chain (cγ‐c cytokines). Twenty‐eight CTL clones were generated from CD8+ T cells obtained from 3 patients during the contraction phase of immune response following a successful vaccine mediated expansion of specific effectors. All clones were able to kill tumor cell lines expressing HLA‐A0201 and Melan‐A/MART‐1, and displayed phenotypic characteristics of effector/memory (CD45RA−/CCR7−) or CD45RA+/CCR7− effector cells in intermediate to late developmental stage (CD28−/CD276±) CTL. Proliferative responses could be elicited or enhanced by IL‐2 and IL‐15, but not IL‐7, in the absence or in the presence of T‐cell receptor (TCR) triggering, respectively. Accordingly, only IL‐2 and IL‐15 were able to promote the survival of the CTL clones under investigation. While all clones expressed high amounts of receptor cγ‐c (CD132), lower, but detectable, expression of IL‐7 receptor alpha chain was also observed. CD8+ cells from one of the patients treated were obtained 6 months after the last vaccine boost and were cultured in the presence of Melan‐A/MART‐1~27–35~ and each of the 3 cytokines under investigation. Consistent with data from CTL clones, expansion of Melan‐A/MART‐1~27–35~ tetramer positive cells was only observed in the presence of IL‐2 or IL‐15 but not IL‐7. Instead, when CD8+ cells from the same patient were sampled shortly (14 days) after an additional vaccination only IL‐2 was able to promote the expansion of Melan‐A/MART‐1~27–35~ tetramer positive cells. Taken together these data suggest a selective responsiveness of TAA‐specific CTL to different cγ‐c cytokines. © 2005 Wiley‐Liss, Inc.