Platelets subvert T cell immunity against cancer via GARP-TGFβ axis.

ABSTRACT: Cancer-associated thrombocytosis has long been linked to poor clinical outcome, but the underlying mechanism is enigmatic. We hypothesized that platelets promote malignancy and resistance to therapy by dampening host immunity. We show that genetic targeting of platelets enhances adoptive T cell therapy of cancer. An unbiased biochemical and structural biology approach established transforming growth factor β (TGFβ) and lactate as major platelet-derived soluble factors to obliterate CD4⁺ and CD8⁺ T cell functions. Moreover, we found that platelets are the dominant source of functional TGFβ systemically as well as in the tumor microenvironment through constitutive expression of the TGFβ-docking receptor glycoprotein A repetitions predominant (GARP) rather than secretion

SUBMITTER: Rachidi S 

PROVIDER: S-EPMC5539882 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature