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Procoagulant platelets promote immune evasion in triple negative breast cancer.

Johanna SchaubaecherBojan SmiljanovFlorian HaringKatja SteigerZhengquan WuAnais UgurluogluJoshua LuftSimone BallkeShaan MahameedVera SchneewindJonas HildingerMartin CanisLaura MittmannConstanze BraunGabriele ZuchtriegelRainer W J KaiserLeo NicolaiMatthias MackWilko WeichertKirsten LauberBernd UhlChristoph A Reichel
Published in: Blood (2024)
Triple-negative breast cancer (TNBC) is an aggressive tumor entity, in which immune checkpoint (IC) molecules are primarily synthesized in the tumor environment. Here, we report that procoagulant platelets bear large amounts of such immunomodulatory factors and that the presence of these cellular blood components in TNBC relates to pro-tumorigenic immune cell activity and impaired survival. Mechanistically, tumor-released nucleic acids attract platelets into the aberrant tumor microvasculature where they undergo procoagulant activation, thus delivering specific stimulatory and inhibitory IC molecules. This concomitantly promotes pro-tumorigenic myeloid leukocyte responses and compromises anti-tumorigenic lymphocyte activity, ultimately supporting tumor growth. Interference with platelet-leukocyte interactions prevented immune cell misguidance and suppressed tumor progression, nearly as effective as systemic IC inhibition. Hence, our data uncover a self-sustaining mechanism of TNBC in utilizing platelets to misdirect immune cell responses. Targeting this irregular multicellular interplay might represent a novel immunotherapeutic strategy in TNBC without side effects of systemic IC inhibition.
Keyphrases
  • peripheral blood
  • dendritic cells
  • acute myeloid leukemia
  • poor prognosis
  • immune response
  • drug delivery
  • electronic health record
  • long non coding rna
  • anti inflammatory
  • red blood cell