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Dendritic cells as mediators of tumor‐induced tolerance in metastatic melanoma
Author(s) -
Enk Alexander H.,
Jonuleit Helmut,
Saloga Joachim,
Knop Jürgen
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971104)73:3<309::aid-ijc1>3.0.co;2-3
Subject(s) - metastatic melanoma , melanoma , dendritic cell , medicine , cancer research , tumor cells , immunology , pathology , biology , immune system
Escape from immune surveillance is critical for tumor progression in metastatic melanoma. We assessed the function of melanoma‐derived dendritic cells (DCs) in patients presenting simultaneously with responding (rM) or progressing (pM) melanoma metastases. These rare coincidences allowed us to compare syngeneically the function of tumor DCs. CD83 + DCs were purified freshly from large responding (rDCs) or progressing (pDCs) metastases following chemo‐immunotherapy. rDCs were 5 times more potent inducers of allogeneic T‐cell proliferation than the pDCs that were used as control. Phenotypic analysis showed a marked depression of CD86 expression on pDCs. Culture supernatants from pM showed production of Th2‐type cytokines [interleukin‐10 (IL‐10)], whereas a Th1 pattern [IL‐2], interferon‐γ (IFN‐γ), IL‐12) predominated in rM. The IL‐10 detected in progressing metastases was directly derived from melanoma cells. Culture supernatants from metastases applied to DC‐supported allo‐MLR assays suppressed T‐cell responses by 50–75% in the case of pM, but not rM. Finally, in a co‐stimulation‐dependent anti‐CD3 tolerance assay, pDCs (but not rDCs) induced anergy in syngeneic CD4 + T cells. Anergy could be overcome by addition of IL‐12 or IL‐2. Our results show that melanoma‐derived factors convert DC‐antigen presenting cell function to tolerance induction against tumor tissue, changing tumor DCs to “silencers” of anti‐tumoral immune responses. Int. J. Cancer 73:309–316, 1997. © 1997 Wiley‐Liss, Inc.