PMC

Treatment history. Timeline, therapy, and response to regimen from presentation of metastatic disease to present.

Surface representation of PD-1 binding interfaces: (A) with PD-L1: orange and yellow represent key hydrophilic and hydrophobic residues, respectively. (B) with pembrolizumab: blue and light green represent key hydrophilic and hydrophobic residues respectively. (C) with nivolumab: magenta and light pink represent key hydrophilic and hydrophobic residues respectively.

Response to therapy monitored by computed tomography. (A) Neck lesion and surrounding lymph nodes: (1) Before BRAFi treatment (January 2014). (2) Recurrence of melanoma after BRAFi treatment (December 2014). (3) After anti-CTLA-4 treatment (April 2015). (B) Pulmonary lesions: (1) After nivolumab and before pembrolizumab treatment (August 2015). (2) During pembrolizumab treatment (March 2016). (3) During pembrolizumab treatment (April 2018). (C) Spleen lesions: (1) Before pembrolizumab treatment (October 2015, size 3.5 cm). (2) During pembrolizumab treatment. (March 2016, size 3 cm). (3) During pembrolizumab treatment (April 2018, size 1.5 cm).

Immunohistochemical staining of the neck, lymph node, and spleen lesions. (A) Visualization of PD-L1 expression in the neck and lymph node lesions before combination therapy with BRAF and MEK inhibitors (December 3, 2013). The areas circled with red dashed lines indicate the presence of immune cells (IM) adjacent to tumor cells (T). Moderate expression of PD-L1 appears in both immune cells and tumor cells. (B) Colocalization of PD-L1 and macrophage marker CD68 in the neck lesion. Several tumor infiltrating macrophages (black arrows) also express PD-L1. (C) Visualization of PD-L1 expression in the neck and spleen lesions from the same patient resistant to a combination therapy with BRAF and MEK inhibitors (September 4, 2015). High levels of PD-L1 are present in tumor infiltrating immune cells and tumor cells. (D) Same observation as panel B above, from the 2015 sample of the neck lesion.