Intratumoral Platelets: Harmful or Incidental Bystanders of the Tumor Microenvironment?

SIMPLE SUMMARY: The tumor microenvironment (TME) is the complex and heterogenous ecosystem of solid tumors known to influence their growth and their progression. Besides tumor cells, the TME comprises a variety of host-derived cell types, ranging from endothelial cells to fibroblasts and immune cells. Clinical and experimental data are converging to indicate that platelets, originally known for their fundamental hemostatic function, also participate in tumor development and shaping of the TME. Considering the abundance of antiplatelet drugs, understanding if and how platelets contribute to the TME may lead to new therapeutic tools for improved cancer prevention and treatments. ABSTRACT: The tumor microenvironment (TME) has gained considerable interest because of its decisive impact on cancer progression, response to treatment, and disease recurrence. The TME can favor the proliferation, dissemination, and immune evasion of cancer cells. Likewise, there is accumulating evidence that intratumoral platelets could favor the development and aggressiveness of solid tumors, notably by influencing tumor cell phenotype and shaping the vascular and immune TME components. Yet, in contrast to other tumor-associated cell types like macrophages and fibroblasts, platelets are still often overlooked as components of the TME. This might be due, in part, to a deficit in investigating and reporting the presence of platelets in the TME and its relationships with cancer characteristics. This review summarizes available evidence from clinical and animal studies supporting the notion that tumor-associated platelets are not incidental bystanders but instead integral and active components of the TME. A particular emphasis is given to the description of intratumoral platelets, as well as to the functional consequences and possible mechanisms of intratumoral platelet accumulation.