The Role of NETs in the Perioperative Tumor Microenvironment

Presenter: Christof Kaltenmeier (advisors: Dr. Samer Tohme)

Summary: Neutrophil extracellular traps (NETs) have recently been implicated in the growth of tumors; however, their impact on immune cells within the tumor microenvironment (TME) remain incompletely understood. Dr. Kaltenmeier's group hypothesizes that NETs can directly interact with infiltrating T cells to promote an immunosuppressive TME. They performed liver ischemia/reperfusion (I/R) in an established colorectal cancer metastasis model to induce NET formation in the TME. In this NET-rich TME, they discovered elevated levels of phenotypically and functionally exhausted T cells. In vitro, NETs contained the immunosuppressive ligand PD-L1 reponsible for T cell exhaustion; an effect abrogated by using PD-L1 KO NETs. NETs were targeted in vivo by treating mice with DNAse or anti-PD-L1 at time of I/R. Treatment caused decreased metastatic burden, decreased NET formation and higher levels of functioning non-exhausted T cells. This mechanism of T cell suppression by NETs represents a viable target for sustaining immune competence within the TME.