Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Immunotherapy vol.2: Desperately looking for hot tumors (#122)

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

Cancer immunotherapy has become the new fourth pillar of cancer treatment (along with surgery, radiotherapy and chemo/targeted therapy). Despite the recent success of novel therapies, only a subgroup of patients show sustained responses. The majority of patients do not respond or acquire resistance over the course of therapy. Thus there is an unmet need to develop new strategies improving the survival of cancer patients. The c-MET receptor tyrosine kinase and its ligand HGF regulate tumor growth and immune functions. Currently, c-MET inhibitors are used to target oncogenic signaling in tumor cells, but little is known about their effects on immune cells during cancer immunotherapy. Here we show that concomitant c-MET inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in mouse cancer models by increasing effector T cell infiltration in tumors. This therapeutic effect was independent of tumor cell-intrinsic c-MET dependence. Mechanistically, we discovered that c-MET inhibition impaired the reactive mobilization and recruitment of neutrophils into tumors and draining lymph nodes in response to cytotoxic immunotherapies. There, in T cell-inflamed microenvironments, neutrophils rapidly acquired immunosuppressive capacities and restrained T cell expansion and effector functions. Increasing serum HGF levels also correlated with increasing neutrophil counts and a poor efficacy of checkpoint blockade in patients. Our work suggests that c-MET inhibitor co-treatment may improve cancer immunotherapies.