Oral Presentation ASDR-AWTRS-MEPSA 2018 Joint Meeting

c-MET+ neutrophils limit melanoma immunotherapy (#52)

Tobias Bald 1
  1. QIMR Berghofer, Herston, QLD, Australia

The receptor tyrosine kinase c-MET and its ligand HGF have emerged as critical drivers of resistance to oncogenic kinase inhibitors in various types of human cancers including melanoma. Currently, c-MET inhibitors (METi) are used to target oncogenic HGF/c-MET signalling in cancer cells. However, the HGF/c-MET axis is also known to modulate immune responses. Using preclinical relevant mouse models of cancer treated with immune checkpoint inhibitors we report here that HGF/c-MET signalling orchestrates an immunosuppressive neutrophil response which limits the efficacy of anti-tumoural T cells. c-MET+ neutrophils acquired an immunosuppressive phenotype in the tumour draining lymph node and the tumour upon immunotherapy. Concurrent adjuvant METi treatment decreased the number of immunosuppressive neutrophils in lymph nodes and tumors associated with an increased number of tumour-specific T cells leading to a significantly improved overall survival. Our experimental work provides a rationale to further evaluate the importance of an immunosuppressive neutrophil response driven by HGF/c-MET signalling in human cancer patients upon immunotherapy.