Immunotherapy is a cornerstone in the treatment of melanoma, and is intended to modulate the host immunity against the tumor. Immunotherapy can be used in an adjuvant setting, after complete surgical excision in patients with a high risk of disease relapse and as a treatment in advanced (unresectable or metastatic) stages. Development of novel therapeutic approaches and the optimization of existing therapies hold a great promise in the field of melanoma therapy research. Different clinical trials are ongoing, and immunotherapy is showing the ability to confirm durable clinical benefits in selected groups of melanoma patients. The aim of this review is to summarize different types of immunotherapy agents, as well as to discuss different strategies, complementary regimens, and possible biomarkers of response to the treatment.
(12.6 5 0.9 in-gel vs. 18.2 5 0.9 load-free, p<0.001), demonstrating a ''knock-down factor'' of 31% when the myocyte is pulling mechanical load. Contraction departure and return velocities were significantly slower in-gel than in the load-free state as expected. However, the systolic calcium transient was greater in-gel than load-free (Fura-2 fluorescence ratio peak height 1.47 5 0.09 in-gel vs. 0.87 5 0.04 load-free, p<0.0001), revealing the mechano-chemotransduction that translates external stress to intracellular Ca 2þ increase. The calcium transient departure and return velocities were also significantly higher in-gel than load-free. Conclusions: Our newly-developed versatile Cell-in-Gel system provides a novel experimental method to control mechanical stress at the single cell level for investigating mechano-chemotransduction pathways in intact myocytes. The above experimental results are consistent with our modeling predictions, demonstrating the mechanical load effects on altering myocyte Ca 2þ handling and contraction dynamics.
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