Figure 3.

Fc receptors are highly expressed in myeloid cells and can impact the cellular biodistribution of an anti-PD1 therapeutic antibody. A) Single-cell RNAseq data from >4,500 cells of melanoma biopsies was clustered according to gene-expression (and thus cell-type), and expression of PD1 and FcγR2b are shown by green color. In this patient cohort, expression of the target of nivolumab, an IgG4 anti-PD1 antibody, is primarily found in T-cells, while its inhibitory Fc receptor FcγR2b is primarily found in B-cells and myeloid cells, including MΦ. Figure adapted with permission from ¹¹ using scRNAseq data GSE72056 ²⁸, copyright 2020. B) Average expression values corresponding to single-cell data in A. C) Immunohistochemistry of a melanoma metastasis to the pancreas shows high FcγR2b expression in cells consistent with infiltrating myeloid cells (from the Human Protein Atlas v19.3 ¹⁹⁵). D) 30 minute time-lapse microscopy of co-culture using PD1+ T-cells, MΦ, and anti-PD1 antibody shows transfer of antibody to MΦ from T-cells that were pre-treated with the antibody, in a FcγR2/3 dependent manner. Scale bar 10 μm. Adapted with permission from ⁸⁰, copyright 2017.