TY - JOUR AU - Bowers, Jacob S. AU - Nelson, Michelle H. AU - Majchrzak, Kinga AU - Bailey, Stefanie R. AU - Rohrer, Baerbel AU - Kaiser, Andrew D.M. AU - Atkinson, Carl AU - Gattinoni, Luca AU - Paulos, Chrystal M. T1 - Th17 cells are refractory to senescence and retain robust antitumor activity after long-term ex vivo expansion PY - 2017/03/09/ AB - Adoptive immunotherapy for solid tumors relies on infusing large numbers of T cells to mediate successful antitumor responses in patients. While long-term rapid-expansion protocols (REPs) produce sufficient numbers of CD8+ T cells for treatment, they also cause decline in the cell’s therapeutic fitness. In contrast, we discovered that IL-17–producing CD4+ T cells (Th17 cells) do not require REPs to expand 5,000-fold over 3 weeks. Also, unlike Th1 cells, Th17 cells do not exhibit hallmarks of senescence or apoptosis, retaining robust antitumor efficacy in vivo. Three-week-expanded Th17 cells eliminated melanoma as effectively as Th17 cells expanded for 1 week when infused in equal numbers into mice. However, treating mice with large recalcitrant tumors required the infusion of all cells generated after 2 or 3 weeks of expansion, while the cell yield obtained after 1-week expansion was insufficient. Long-term-expanded Th17 cells also protected mice from tumor rechallenge including lung metastasis. Importantly, 2-week-expanded human chimeric antigen receptor–positive (CAR+) Th17 cells also retained their ability to regress human mesothelioma, while CAR+ Th1 cells did not. Our results indicate that tumor-reactive Th17 cells are an effective cell therapy for cancer, remaining uncompromised when expanded for a long duration owing to their resistance to senescence. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.90772 VL - 2 IS - 5 UR - https://doi.org/10.1172/jci.insight.90772 PB - The American Society for Clinical Investigation ER -