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Review
. 2019 May 8;11(5):639.
doi: 10.3390/cancers11050639.

TRAIL and FasL Functions in Cancer and Autoimmune Diseases: Towards an Increasing Complexity

Aurélie Rossin  1 , Giorgia Miloro  2 , Anne-Odile Hueber  3
Affiliations
Review

TRAIL and FasL Functions in Cancer and Autoimmune Diseases: Towards an Increasing Complexity

Aurélie Rossin et al. Cancers (Basel). .

Abstract

Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10) and Fas Ligand (FasL/TNFSF6), two major cytokines of the TNF (Tumor Necrosis Factor) superfamily, exert their main functions from the immune system compartment. Mice model studies revealed that TRAIL and FasL-mediated signalling both control the homeostasis of the immune cells, mainly from the lymphoid lineage, and function on cytotoxic cells as effector proteins to eliminate the compromised cells. The first clues in the physiological functions of TRAIL arose from the analysis of TRAIL deficient mice, which, even though they are viable and fertile, are prone to cancer and autoimmune diseases development, revealing TRAIL as an important safeguard against autoimmunity and cancer. The naturally occurring gld (generalized lymphoproliferative disease) and lpr (lymphoproliferation) mutant mice develop lymphadenopathy and lupus-like autoimmune disease. The discovery that they are mutated in the fasl and the fas receptor gene, respectively, demonstrates the critical role of the FasL/Fas system in lymphocyte homeostasis and autoimmunity. This review summarizes the state of current knowledge regarding the key death and non-death immune functions that TRAIL and FasL play in the initiation and progression of cancer and autoimmune diseases.

Keywords: autoimmunity; cancer; cell death; death receptors; immune system.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
TRAIL and FasL activities in the control of autoimmunity. Whereas, TRAIL acts as a guardian against autoimmunity, FasL exerts both a role of guardian, but also promoter of autoimmunity. The main respective roles of their death (highlighted in green) and non-death (highlighted in pink) functions are represented. APC is for antigen presenting cells, DC for dendritic cells, and Act T cell for activated T cells.
Figure 2
Figure 2
TRAIL and FasL pro- and anti-tumoral activities within the tumor nest. The main respective roles of their death (highlighted in green) and non-death (highlighted in pink) functions are represented. Briefly, TRAIL and FasL, mainly from tumor-infiltrating lymphocytes (TIL) and natural killer (NK) cells origin target the different cells of the tumor nest. They trigger the death of immunosuppressive cells such as regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). The tumor cells can respond either by death but also non death pro tumoral functions which lead to tumor escape. Moreover, the tumor can escape from the immune system by specific killing of the TIL through abnormal expression of FasL on stromal cells.
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