Abstract
The sphingolipid sphingosine-1-phosphate (S1P) promotes tumor development through a variety of mechanisms including promoting proliferation, survival, and migration of cancer cells. Moreover, S1P emerged as an important regulator of tumor microenvironmental cell function by modulating, among other mechanisms, tumor angiogenesis. Therefore, S1P was proposed as a target for anti-tumor therapy. The clinical success of current cancer immunotherapy suggests that future anti-tumor therapy needs to consider its impact on the tumor-associated immune system. Hereby, S1P may have divergent effects. On the one hand, S1P gradients control leukocyte trafficking throughout the body, which is clinically exploited to suppress auto-immune reactions. On the other hand, S1P promotes pro-tumor activation of a diverse range of immune cells. In this review, we summarize the current literature describing the role of S1P in tumor-associated immunity, and we discuss strategies for how to target S1P for anti-tumor therapy without causing immune paralysis.
Highlights
Cancer is a collective term for more than 100 diseases that are defined by the uncontrolled multiplication of cells and the invasion of these transformed cells into other parts of their tissue of origin, or into other tissues
S1PR2 is expressed during inflammation with S1PR1 being upregulated during its resolution to facilitate their emigration from the site of inflammation [106,107]
An induction of natural killer T (NKT) cell activation was observed under these conditions accompanied by an increase in the NKT cell lipid antigen cardiolipin upon sphingosine kinase-1 (SPHK1) ablation [132]
Summary
Cancer is a collective term for more than 100 diseases that are defined by the uncontrolled multiplication of cells and the invasion of these transformed cells into other parts of their tissue of origin, or into other tissues. Cancer is a genetic disease triggered by somatic mutations in cells, but the origins of these mutations are multifactorial with only about 5–10% being germline inherited genetic defects, while the remaining 90–95%. While the contribution of some of these factors to overall mortality is in decline, the contribution of others, such as diet and its associated morbidities, e.g., obesity, are on the rise [4]. This indicates that the incidence of cancers related to the latter issues may increase in the coming years.
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