The wolf in sheep's clothing: Platelet-derived "pseudo self" impairs cancer cell "missing self" recognition by NK cells

Abstract

Metastasis is strongly inhibited in thrombocytopenic mice. This phenotype is reversed by NK cell depletion which indicates that platelets may facilitate tumor progression and metastasis by interfering with NK cell immunosurveillance. Understanding the underlying mechanisms may help us to reinforce anti-tumor immunity and NK-based immunotherapy in cancer patients.

Figure 1. The role of platelet-derived “pseudo-self” in tumor immune evasion. (A) T cell immunity is mediated by recognition of tumor antigens presented by the tumor cell’s own MHC Class I; the latter at the same time inhibits NK cell reactivity. (B) MHC Class I downregulation enables escape from T cell immunity but renders tumor cells susceptible to NK “missing self” recognition. (C) Transfer of platelet MHC Class I results in a “pseudo-self” phenotype which impairs NK immunosurveillance by concealing the “missing self” without inducing T cell reactivity due to presentation of “unsuspicious” peptides.