qualitative-quantitative-analysis-immune-synapse-human-system-using

Qualitative and Quantitative Analysis of the Immune Synapse in the Human System Using Imaging Flow Cytometry

The immune synapse is the area of communication between T cells and antigen-presenting cells (APCs). T cells polarize surface receptors and proteins ...

University of Heidelberg

Ectopic expression of L-plastin in human tumor cells: diagnostic and therapeutic implications.

Tumor cell migration and metastasis require dynamic rearrangements of the actin cytoskeleton. Interestingly, the F-actin cross-linking and stabilizing protein L-plastin, originally described as a leukocyte specific protein, is aberrantly expressed in several non-hematopoietic malignant tumors. Therefore, it has been discussed as a tumor marker. However, systematic in vivo analyses of the functional relevance of L-plastin for tumor cell metastasis were so far lacking.

Metastasis of prostate cancer and melanoma cells in a preclinical in vivo mouse model is enhanced by L-plastin expression and phosphorylation.

Sulforaphane (SFN) is a naturally occurring isothiocyanate derived from cruciferous vegetables such as broccoli. It has been reported to inhibit the growth of a variety of cancers, such as breast, prostate, colon, skin, lung, gastric or bladder cancer. SFN is supposed to act primarily as an antioxidant due to the activation of the Nrf2-Keap1 signaling pathway. This enhances the activity of phase II detoxifying enzymes and the trapping of free radicals. Finally, SFN induces cell cycle arrest or apoptosis of tumor cells. Here, we discuss effects of SFN on the immune defense system. In contrast to the situation in tumor cells, SFN acts pro-oxidatively in primary human T cells. It increases intracellular ROS levels and decreases GSH, resulting in inhibition of T cell activation and T cell effector functions. Regarding the use of SFN as an "anticancer agent" we conclude that SFN could act as a double-edged sword. On the one hand it reduces carcinogenesis, on the other hand it blocks the T cell-mediated immune response, the latter being important for immune surveillance of tumors. Thus, SFN could also interfere with the successful application of immunotherapy by immune checkpoint inhibitors (e.g. CTLA-4 antibodies and PD-1/PD-L1 antibodies) or CAR T cells. Therefore, a combination of SFN with T cell-mediated cancer immunotherapies does not seem advisable.

Article	Year
Ectopic expression of L-plastin in human tumor cells: diagnostic and therapeutic implications. Advances in enzyme regulation\| PubMed ID: 17335876	2007
Metastasis of prostate cancer and melanoma cells in a preclinical in vivo mouse model is enhanced by L-plastin expression and phosphorylation. Molecular cancer\| PubMed ID: 24438191	2014
Sulforaphane as anticancer agent: A double-edged sword? Tricky balance between effects on tumor cells and immune cells. Advances in biological regulation\| PubMed ID: 30528536	2018

Yvonne Samstag

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