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Tumor's other immune targets: dendritic cells
Author(s) -
Esche Clemens,
Lokshin Anna,
Shurin Galina V.,
Gastman Brian R.,
Rabinowich Hannah,
Watkins Simon C.,
Lotze Michael T.,
Shurin Michael R.
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.66.2.336
Subject(s) - apoptosis , biology , tunel assay , dna fragmentation , immune system , annexin , dendritic cell , programmed cell death , cancer research , uvb induced apoptosis , microbiology and biotechnology , caspase , immunology , biochemistry
The induction of apoptosis in T cells is one of several mechanisms by which tumors escape immune recognition. We have investigated whether tumors induce apoptosis in dendritic cells (DC) by co‐culture of murine or human DC with different tumor cell lines for 4–48 h. Analysis of DC morphological features, JAM assay, TUNEL, caspase‐3‐like and transglutaminase activity, Annexin V binding, and DNA fragmentation assays revealed a time‐ and dose‐dependent induction of apoptosis in DC by tumor‐derived factors. This finding is both effector and target specific. The mechanism of tumor‐induced DC apoptosis involved regulation of Bcl‐2 and Bax expression. Double staining of both murine and human tumor tissues confirmed that tumor‐associated DC undergo apoptotic death in vivo. DC isolated from tumor tissue showed significantly higher levels of apoptosis as determined by TUNEL assay when compared with DC isolated from spleen. These findings demonstrate that tumors induce apoptosis in DC and suggest a new mechanism of tumor escape from immune recognition. DC protection from apoptosis will lead to improvement of DC‐based immunotherapies for cancer and other immune diseases. J. Leukoc. Biol. 66: 336–344; 1999.