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

• DOI: 10.1126/sciimmunol.aai7911
• Publication Date: 2017-05-06T00:50:33Z
• Authors: Saleh Rachidi; Alessandra Metelli; Brian Riesenberg; Bill X. Wu; Michelle H. Nelson; Caroline Wallace; Chrystal M. Paulos; Mark P. Rubinstein; Elizabeth Garrett...; Mirko Hennig; Daniel W. Bearden; Yi Yang; Bei Liu; Zihai Li
• Keywords: Cancer Immunotherapy

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 therapy by dampening host immunity. show genetic targeting of enhances adoptive T cell cancer. An unbiased biochemical structural biology approach established transforming growth factor β (TGFβ) lactate as major platelet-derived soluble factors obliterate CD4+ CD8+ functions. Moreover, we found are dominant source functional TGFβ systemically well in tumor microenvironment through constitutive expression TGFβ-docking receptor glycoprotein A repetitions predominant (GARP) rather than secretion per se. Platelet-specific deletion GARP-encoding gene Lrrc32 blunted activity at site potentiated protective immunity against both melanoma colon Last, this study shows cancer can be substantially improved concurrent treatment with readily available antiplatelet agents. conclude constrain a GARP-TGFβ axis suggest combination immunotherapy platelet inhibitors therapeutic strategy