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Selective responsiveness to common gamma chain cytokines in peripheral blood-derived cytotoxic T lymphocytes induced by Melan-A/MART-1(27-35)targeted active specific immunotherapy.
- Source :
-
International journal of cancer [Int J Cancer] 2005 Jun 10; Vol. 115 (2), pp. 248-55. - Publication Year :
- 2005
-
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 gamma-chain (c gamma-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 c gamma-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 c gamma-c cytokines.<br /> (Copyright 2005 Wiley-Liss, Inc)
- Subjects :
- Antigens, Neoplasm immunology
Antigens, Neoplasm metabolism
Cell Proliferation
HLA-A Antigens metabolism
HLA-A2 Antigen
Humans
Immunologic Memory
Interleukin-15 immunology
Interleukin-15 metabolism
Interleukin-2 immunology
Interleukin-2 metabolism
Interleukin-7 immunology
Interleukin-7 metabolism
MART-1 Antigen
Receptors, Antigen, T-Cell immunology
Receptors, Antigen, T-Cell metabolism
Receptors, Interleukin-7 metabolism
Skin Neoplasms immunology
Skin Neoplasms secondary
Tumor Cells, Cultured
CD8-Positive T-Lymphocytes immunology
Immunotherapy
Melanoma immunology
Melanoma secondary
Melanoma therapy
Neoplasm Proteins immunology
Skin Neoplasms therapy
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0020-7136
- Volume :
- 115
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 15688403
- Full Text :
- https://doi.org/10.1002/ijc.20858