Hiding in Plain Sight: Soluble Immunomodulatory Receptors.

Alternatively spliced natural soluble isoforms of immunomodulatory receptors [cytotoxic T lymphocyte antigen-4 (CTLA-4), 4-1BB, and programmed death-1 (PD-1)/PD-L1] have been overlooked in favor of their cell-surface-bound counterparts that have generated blockbuster antibodies for the treatment of cancer. We propose that the soluble variants of these receptors contribute to immune regulation and offer potential as targets for immunotherapy.