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Interactions of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) with the Immune System: Implications for Inflammation and Cancer

Charité-Universitätsmedizin Berlin, Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1161;
Received: 30 June 2019 / Revised: 7 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
(This article belongs to the Special Issue TRAIL Signaling in Cancer Cells)
PDF [2344 KB, uploaded 19 August 2019]


Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL has historically been distinct from the Fas ligand and TNFα in terms of selective apoptosis induction in tumor cells and has a nearly non-existent systemic toxicity. Consequently, in the search for an ideal drug for tumor therapy, TRAIL rapidly drew interest, promising effective tumor control with minimal side effects. However, euphoria gave way to disillusionment as it turned out that carcinoma cells possess or can acquire resistance to TRAIL-induced apoptosis. Additionally, studies on models of inflammation and autoimmunity revealed that TRAIL can influence immune cells in many different ways. While TRAIL was initially found to be an important player in tumor defense by natural killer cells or cytotoxic T cells, additional effects of TRAIL on regulatory T cells and effector T cells, as well as on neutrophilic granulocytes and antigen-presenting cells, became focuses of interest. The tumor-promoting effects of these interactions become particularly important for consideration in cases where tumors are resistant to TRAIL-induced apoptosis. Consequently, murine models have shown that TRAIL can impair the tumor microenvironment toward a more immunosuppressive type, thereby promoting tumor growth. This review summarizes the current state of knowledge on TRAIL’s interactions with the immune system in the context of cancer. View Full-Text
Keywords: TRAIL; apoptosis; cancer; inflammation; immune system TRAIL; apoptosis; cancer; inflammation; immune system

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Beyer, K.; Baukloh, A.-K.; Stoyanova, A.; Kamphues, C.; Sattler, A.; Kotsch, K. Interactions of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) with the Immune System: Implications for Inflammation and Cancer. Cancers 2019, 11, 1161.

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