Cutting Edge: The Tumor Counterattack Hypothesis Revisited: Colon Cancer Cells Do Not Induce T Cell Apoptosis Via the Fas (CD95, APO-1) Pathway

Favre-Félix, Nathalie; Fromentin, Annie; Hammann, Arlette; Solary, Éric; Martin, François; Bonnotte, Bernard

doi:10.4049/jimmunol.164.10.5023

Cited by 69 publications

(43 citation statements)

References 24 publications

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“…The T lymphocytes underwent apoptosis following coculture with FasL-expressing rat hippocampal neurons, but only a minority of the T lymphocytes were rescued by inhibiting the Fas-FasL interaction with Abs (18). Other work showed that several T cell lines do not undergo apoptosis after confrontation with FasL-expressing tumors or APCs (22,23), also suggesting a distinct mechanism for the FasL-dependent immunodeviation observed in vivo (21).…”

Section: Discussionmentioning

confidence: 97%

Fas Ligand (CD95L) Protects Neurons Against Perforin- Mediated T Lymphocyte Cytotoxicity

Medana

Flügel

et al. 2001

The Journal of Immunology

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Previous work showed that neurons of the CNS are protected against perforin-mediated T cell cytotoxicity, but are susceptible to Fas-mediated apoptosis. In this study, we report that Fas ligand (FasL) expression by neurons is involved in protection against perforin-mediated T cell cytotoxicity. Gene transcripts for FasL were identified in single murine hippocampal neurons by RT-PCR combined with patch clamp electrophysiology, and constitutive expression of FasL protein was confirmed in neurons by immunohistochemistry. Neurons derived from wild-type C57BL/6 (BL6) mice and mutant BL6.gld mice lacking functional FasL were confronted with allogeneic CTLs and continuously monitored in real time for changes in levels of intracellular calcium ([Ca2+]i), an indicator of cytotoxic damage. Perforin-mediated plasma membrane lysis, characterized by rapid, massive [Ca2+]i influx into the target cells within 0.5 h, was not detected in wild-type neurons. In striking contrast, FasL-deficient neurons showed rapid increase in [Ca2+]i within 0.5 h, reflecting perforin-dependent cell lysis. FasL seems to protect neurons by blocking degranulation of CTLs, since CD3-induced release of cytotoxic granules was reduced by coapplication of Fas-specific Abs or rFasL.

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Section: Discussionmentioning

confidence: 97%

Fas Ligand (CD95L) Protects Neurons Against Perforin- Mediated T Lymphocyte Cytotoxicity

Medana

Flügel

et al. 2001

The Journal of Immunology

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“…20,36 Fas-L detection on some tumor samples has suffered from technical inconsistencies based on unspecific Abs, 28,37 and the lack of Fas-L detection using FACS or RT ± PCR. 21,35,38 We demonstrated Fas-L expression on escape tumor cell lines by FACS analysis, thus avoiding lymphocyte contamination that may contribute to Fas-L detection in fresh tumor samples, by immunohistochemistry using a different antibody both on cytospins and on tumor samples after reinjection in vivo and by RT ± PCR using specific primers and sequencing of the resulting fragment.…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of Fas ligand on tumor cells escaping active specific immunotherapy

et al. 2001

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Mice transgenic for the rat HER-2/neu oncogene (rNeu-TG) developed spontaneous breast tumors that can escape a rNeu-specific immune response induced by active specific immunotherapy (ASI). The ability of these escape tumors to grow appeared to be due to upregulation of the Fas ligand (Fas-L) molecule. In an effort to develop tools for the better elucidation of the role of Fas-L and other regulatory mechanisms in tumor escape, we established cell lines derived from escape tumors. These tumor cell lines retained MHC class I, rNeu and Fas-L expression in vitro and formed tumors in vaccinated mice. Tumor growth was accompanied by permanent Fas-L expression in vivo, both in vaccinated and control vaccinated mice, indicating that these cells have acquired constitutive Fas-L expression. Moreover, these cells induced target cell apoptosis in vitro. Thus, these cells represent a unique tool to elucidate the importance of Fas-L expressed by tumors that escaped efficient systemic immune responses. Cell Death and Differentiation (2001) 8, 687 ± 695.

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“…The 002 hybridoma or D10 Th2 cells were used as killer cells. The targets were A20 mouse B cells or Jurkat human T cells, which constitutively express the Fas receptor and are capable of undergoing Fas-mediated cell death (28,29). To measure the amount of fragmented DNA produced by the target cells but not the killer cells, target cells were labeled with [ 3 H]thymidine.…”

Section: Ciita-expressing Cells Have Reduced Killing Abilitymentioning

confidence: 99%

Cutting Edge: The Class II Transactivator Prevents Activation-Induced Cell Death by Inhibiting Fas Ligand Gene Expression

Gourley

Chang

2001

The Journal of Immunology

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The Fas:Fas ligand pathway is critical in regulating immune homeostasis by eliminating activated T cells that proliferated in response to an infection. Here, we show that the MHC class II transactivator (CIITA) can suppress this pathway by inhibiting transcription of the Fas ligand gene. CIITA can effectively repress transcription from the Fas ligand promoter in both T cell lines as well as primary cells. The repression appears to be at least partly due to interference of NFAT-mediated induction of Fas ligand gene transcription. T cells that express CIITA constitutively do not up-regulate Fas ligand on the cell surface after activation via the TCR. Consequently, these cells lack the ability to undergo activation-induced cell death, and to kill Fas-bearing target cells.

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Cutting Edge: The Tumor Counterattack Hypothesis Revisited: Colon Cancer Cells Do Not Induce T Cell Apoptosis Via the Fas (CD95, APO-1) Pathway

Cited by 69 publications

References 24 publications

Fas Ligand (CD95L) Protects Neurons Against Perforin- Mediated T Lymphocyte Cytotoxicity

Fas Ligand (CD95L) Protects Neurons Against Perforin- Mediated T Lymphocyte Cytotoxicity

Functional characterization of Fas ligand on tumor cells escaping active specific immunotherapy

Cutting Edge: The Class II Transactivator Prevents Activation-Induced Cell Death by Inhibiting Fas Ligand Gene Expression

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