![]() ![]() In attempts to identify how solid tumors avoid immune-mediated destruction, several large-scale immune profiling studies have been performed on different human cancers utilizing various combinations of RNA sequencing, immunohistochemistry (IHC), whole-exome sequencing, flow cytometry, etc. The current study describes what we believe to be a novel mechanism by which ARG1 mRNA expression is regulated in neutrophils in cancer and highlights the central role that neutrophil lineage cells play in the suppression of tumor-infiltrating lymphocytes. Mechanistically, ANXA2 signaled through the TLR2/MYD88 axis in neutrophils to induce ARG1 mRNA expression. These studies identified ANXA2 as the major driver of ARG1 mRNA expression in TANs. To determine the mechanism by which ARG1 mRNA is induced in TANs, we utilized FPLC followed by MS/MS to screen tumor-derived factors capable of inducing ARG1 mRNA expression in neutrophils. ![]() Importantly, we showed that approximately 40% of tumor-associated neutrophils (TANs) actively transcribed ARG1 mRNA. Here, we showed that neutrophil lineage cells and not monocytes or macrophages expressed ARG1 in human non–small cell lung cancer (NSCLC). Despite numerous studies exploring the mechanisms by which ARG1 perturbs lymphocyte function, the cellular populations responsible for its generation and release remain poorly understood. Myeloid lineage cells suppress T cell viability through arginine depletion via arginase 1 (ARG1). ![]()
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