Proximal signaling responses in peripheral T cells from colorectal cancer patients are affected by high concentrations of circulating prostaglandin E2

Abstract Patients with colorectal cancer (CRC) have been shown to have elevated levels of circulating prostaglandin E 2 (PGE 2 ) which promotes cancer progression and suppresses T cell immune responses. In this study we evaluated whether signaling responses in T lymphocytes obtained from peripheral blood of CRC patients were affected by the sustained exposure to increased levels of PGE 2 . The phosphorylation status of an extended panel of proteins involved in downstream signaling cascades in T cells was profiled at a single cell level both in naive and antigen-experienced cells after triggering T cell-, prostaglandin- and interleukin-2 receptors. Peripheral T cells from patients with elevated PGE 2 levels displayed aberrant T cell signaling responses downstream of the T cell receptor (assessed by reduced phosphorylation of CD3ζ and SLP76), and after triggering the IL-2 receptor (assessed by reduced phosphorylation of STAT5) when compared to T cells from CRC patients with lower levels of PGE 2 and T cells from healthy blood donors. This signaling study of circulating T cells from CRC patients indicates that increased systemic PGE 2 levels affect proximal T cell responses and confirms phospho-specific flow cytometry to be a valuable tool for revealing signaling signatures in immunological disorders.