IL-6 fuels durable memory for Th17 cell-mediated responses to tumors

The accessibility of adoptive T cell transfer therapies (ACT) is hindered by cost and time required for product development. Here we describe a streamlined ACT protocol using Th17 cells expanded only four days ex vivo. While shortening expansion compromised cell yield, this method licensed Th17 cells to eradicate large tumors to a greater extent than cells expanded longer term. Day 4 Th17 cells engrafted, induced release of multiple cytokines including IL-6, IL-17, MCP-1, and GM-CSF in the tumor-bearing host, and persisted as memory cells. IL-6 was a critical component for efficacy of these therapies via its promotion of long-term immunity and resistance to tumor relapse. Mechanistically, IL-6 diminished engraftment of FoxP3+ donor T cells, corresponding with robust tumor infiltration by donor effector over regulatory cells for the Day 4 Th17 cell product relative to cell products expanded longer durations ex vivo. Collectively, this work describes a method to rapidly generate therapeutic T cell products for ACT and implicates IL-6 in promoting durable immunity of Th17 cells against large, established solid tumors.