Immature dendritic cells kill ovarian carcinoma cells by a FAS/FASL pathway, enabling them to sensitize tumor-specific CTLs

Yang, Rongcun; Xu, Dawei; Zhang, Anju; Gruber, Astrid

doi:10.1002/ijc.1484

Cited by 39 publications

(34 citation statements)

References 53 publications

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“…Higher levels of FasL expression are not only found on activated T cells but also on cancer-associated dendritic cells and macrophages. 47,48 Similar to CTLs, dendritic cells and macrophages are also important effector cells against tumors. However, based on our discoveries, it can be speculated that dendritic cells and macrophages may be accomplices of CTLs in facilitating tumor escape.…”

Section: Discussionmentioning

confidence: 99%

Activated cytotoxic lymphocytes promote tumor progression by increasing the ability of 3LL tumor cells to mediate MDSC chemoattraction via Fas signaling

et al. 2014

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The Fas/FasL system transmits intracellular apoptotic signaling, inducing cell apoptosis. However, Fas signaling also exerts non-apoptotic functions in addition to inducing tumor cell apoptosis. For example, Fas signaling induces lung cancer tumor cells to produce prostaglandin E2 (PGE2) and recruit myeloid-derived suppressor cells (MDSCs). Activated cytotoxic T lymphocytes (CTLs) induce and express high levels of FasL, but the effects of Fas activation initiated by FasL in CTLs on apoptosis-resistant tumor cells remain largely unclear. We purified activated CD81 T cells from OT-1 mice, evaluated the regulatory effects of Fas activation on tumor cell escape and investigated the relevant mechanisms. We found that CTLs induced tumor cells to secrete PGE2 and increase tumor cell-mediated chemoattraction of MDSCs via Fas signaling, which was favorable to tumor growth. Our results indicate that CTLs may participate in the tumor immune evasion process. To the best of our knowledge, this is a novel mechanism by which CTLs play a role in tumor escape. Our findings implicate a strategy to enhance the antitumor immune response via reduction of negative immune responses to tumors promoted by CTLs through Fas signaling.

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Section: Discussionmentioning

confidence: 99%

Activated cytotoxic lymphocytes promote tumor progression by increasing the ability of 3LL tumor cells to mediate MDSC chemoattraction via Fas signaling

et al. 2014

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“…In addition to the TRAIL-mediated killing activity of DCs, FasL-mediated killing of ovarian carcinoma cells by immature human DCs has been shown. 64 In mice, Shortman's group 69 described the expression of FasL on a subset of CD8 þ DCs that allow them to kill Fas þ activated T cells. A FADD-independent mechanism used by human monocytederived DCs has also been reported.…”

Section: Killer Dcsmentioning

confidence: 99%

The ‘kiss of death’ by dendritic cells to cancer cells

Chan

Housseau

2007

Cell Death Differ

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“…Ascitic monocytes from ovarian cancer patients that are cultured to become mono-DC acquire the ability to kill both autologous and allogeneic ovarian carcinoma cell lines in vitro via a FasL-dependent mechanism. 41 Cord blood-derived mono-DC stimulated with IFN-g can kill the Jurkat (T lymphoma) and HL-60 (myelomonocytic leukemia) tumor cell lines, but not Daudi (Burkitt's lymphoma), tumor cell lines. However, when stimulated with LPS, these DC kill the Daudi and Jurkat, but not the HL-60, target cells.…”

Section: Cultured Kdc Generated From Bone Marrow Progenitor Cells or mentioning

confidence: 99%

“…Indeed, there is preclinical evidence that subsequent to DC-mediated lysis of target cells, these APC engulf antigens from tumor apoptotic bodies, enabling them to cross-prime T-cell responses. 7,13,41 Therapeutic Implications for KDC While formal proof is lacking, if the same cell that kills the tumor takes up the apoptotic body and presents its derivative antigens to T cells in secondary lymphoid organs, the potential convergence of these varied functions in KDC would yield a physiologically-economical/efficient anti-tumor paradigm attractive for clinical translation in the cancer setting. In the context of such a paradigm, two major forms of KDC clinical trials could be immediately envisioned: 1) approaches utilizing ex vivo generated KDC injected into accessible tumor lesions or that would predictably home into tumor lesions after systemic administration; or 2) treatment of cancer patients with modalities that augment KDC function in vivo, particularly within the tumor microenvironment.…”

Section: Crosspriming Of Anti-tumor Immunity By Kdcmentioning

confidence: 99%

Killer dendritic cells: mechanisms of action and therapeutic implications for cancer

Wesa

Storkus

2007

Cell Death Differ

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Dendritic cells (DC) are essential for the development and regulation of adaptive host immune responses against tumors. DC are heterogeneous and comprised of diverse cellular subsets. They are best known for mediating a crucial role in the initiation of acquired immunity by serving as professional antigen presenting cells (APC) that take up antigens in their local microenvironment, which are then processed and presented to naïve T cells in the context of major histocompatibility complex (MHC) class I and II molecules. In addition to these functions, DC can modulate the types of T cell responses they generate, and can also influence the responses of innate effectors, such as NK cells. There is also now evidence that they may mediate a more primordial role as innate, effector cells that are tumoricidal. 'Killer' DC (KDC) may represent a true 'multi-tasking' cell type that can sequentially act as a 'hunter-gatherer' of antigens; as well as, an instructor, then enforcer/regulator, of antigenspecific anti-tumor T-cell responses in vivo. In this review, we will critically examine the published record regarding KDC, their mechanism(s) of action, and then consider the potential integration of KDC into novel immunotherapies for patients with cancer.

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Immature dendritic cells kill ovarian carcinoma cells by a FAS/FASL pathway, enabling them to sensitize tumor-specific CTLs

Cited by 39 publications

References 53 publications

Activated cytotoxic lymphocytes promote tumor progression by increasing the ability of 3LL tumor cells to mediate MDSC chemoattraction via Fas signaling

Activated cytotoxic lymphocytes promote tumor progression by increasing the ability of 3LL tumor cells to mediate MDSC chemoattraction via Fas signaling

The ‘kiss of death’ by dendritic cells to cancer cells

Killer dendritic cells: mechanisms of action and therapeutic implications for cancer

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