It is most clinically meaningful to study the mechanism by which melanoma cells are resistant to immune checkpoint blockade or adoptive cell therapy (tumor-infiltrating lymphocytes). Immunotherapy can come with severe immune-related adverse events, thus, from a diagnosis perspective, identify gene signature of melanoma that are sensitive to immunotherapy is crucial for patient cohort selection. However, it is difficult to rigorously interrogate immune-related questions using human cell lines and in vitro assay. With that said, this can be done using monocytes and T cell lines. While U937 and Jurkat cells are isolated from lymphoma and leukemia, respectively, they still retain antigen presentation and cytotoxic capacity after proper induction. 

Targeted combination therapy-BRAFi (dabrafenib) and MEKi (trametinib)-is not optimal but optional for BRAF+ patients. Given mechanism related to this treatment approach is easier to be tested by human cell lines and in vitro assays, it is clinically relevant to understand how heterogeneity contributes to resistance.