Nadine S. Jahchan, BSc, PhD, and Alicia Levey, BA, PhD, both of Pionyr Immunotherapeutics, San Francisco, CA, presents on targeting of triggering receptor expressed on myeloid cells-2 (TREM2)-positive tumor-associated macrophages (TAMs) to overcome resistance to immune checkpoint inhibitors (ICIs) by tuning the tumor myeloid microenvironment (TME) in patients with solid tumors. The transmembrane protein TREM2 was identified as a highly enriched TAMs target and TREM2 mRNA expression was found to negatively correlate with patient survival. An anti-TREM2 monoclonal antibody therapy named PY314 was developed which demonstrated anti-tumor activity in ICI-sensitive models as a single agent, and in ICI-resistant tumor models when used in combination with anti-PD-1. An immunohistochemistry assay has been developed to assess TREM2 expression levels and to help identify patients most likely to benefit from PY314 therapy. This interview took place at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.