Profiling of tumor-infiltrating natural killer (NK) cells and macrophages in untreated C57BL/6 mice and mice treated with combination immunotherapies

Treatments aiming to augment immune checkpoint blockade (ICB) in cancer often focus on T cell immunity, but innate immune cells may have important roles to play. Here we demonstrate a single-dose combination treatment (termed AIP) employing a pan-tumor-targeting antibody surrogate, half-life-extended interleukin-2 (IL-2), and anti-PD-1, which primes tumors to respond to subsequent ICB and promotes rejection of large established tumors in mice. NK cells and macrophages activated by AIP treatment underwent transcriptional reprogramming, rapidly killed cancer cells, governed the recruitment of cross-presenting dendritic cells (DCs) and other leukocytes, and induced normalization of the tumor vasculature, facilitating further immune infiltration. In order to parse out the contribution of each components in the 1X AIP treatment, we examined NK cells and macrophages from B16F10-bearing mice treated with AIP, AI, IP and AP or left untreated. Overall design: Examination of tumor-infiltrating natural killer cells or macrophages from untreated C57BL/6 mice or mice treated with AP, IP, AI, or AIP drug combinations.