UNDERSTANDING NEUTROPHIL HETEROGENEITY DURING CANCER

Abstract

It is well established that neutrophils play an important role in cancer progression through the interaction with the complex tumor microenvironment. As neutrophils can display varying phenotypes during cancer progression, it highlights the fact that these cells exist as a heterogenous population in the tumor. Using our established orthotopic pancreatic tumor model and multiomic approaches, we identified three tumor neutrophil subsets (T1, T2 and T3) that were uniquely found only in the tumor. Large-scale proteomic screening identified dcTRAIL-R1 as a potential surface marker to distinguish immunosuppressive T3 neutrophils. Interestingly, neutrophils were able to upregulate this surface marker only in the tumor and is likely cancer-driven. Functional analysis further revealed that T3 neutrophils have the highest Arginase 1 activity, which explained the greatest reduction of their T cell co-stimulation ability when in the tumor. Thus, our study identifies immunosuppressive dcTRAIL-R1+ T3 neutrophils in the neutrophil heterogeneous population within the tumor microenvironment.