2. Academic Validation
  3. IL6 Fuels Durable Memory for Th17 Cell-Mediated Responses to Tumors

IL6 Fuels Durable Memory for Th17 Cell-Mediated Responses to Tumors

  • Cancer Res. 2020 Sep 15;80(18):3920-3932. doi: 10.1158/0008-5472.CAN-19-3685.
Hannah M Knochelmann 1 2,  Connor J Dwyer 3 2,  Aubrey S Smith 3 2,  Jacob S Bowers 3 2,  Megan M Wyatt 3 2,  Michelle H Nelson 3 2,  Guillermo O Rangel Rivera 3 2,  Joshua D Horton 3,  Carsten Krieg 3,  Kent Armeson 4,  Gregory B Lesinski 5,  Mark P Rubinstein 3 6,  Zihai Li 7,  Chrystal M Paulos 1 2
Affiliations

Affiliations

  • 1 Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, South Carolina. knochelm@musc.edu chrystal.mary.paulos@emory.edu.
  • 2 Department of Dermatology & Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
  • 3 Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, South Carolina.
  • 4 Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina.
  • 5 Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia.
  • 6 Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.
  • 7 Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio.
PMID: 32561531 DOI: 10.1158/0008-5472.CAN-19-3685
Abstract

The accessibility of adoptive T-cell transfer therapies (ACT) is hindered by the cost and time required for product development. Here we describe a streamlined ACT protocol using Th17 cells expanded only 4 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 IL6, IL17, MCP-1, and GM-CSF in the tumor-bearing host, and persisted as memory cells. IL6 was a critical component for efficacy of these therapies via its promotion of long-term immunity and resistance to tumor relapse. Mechanistically, IL6 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 IL6 in promoting durable immunity of Th17 cells against large, established solid tumors. SIGNIFICANCE: An abbreviated, 4-day ex vivo expansion method licenses Th17 cells to confer long-lived immunity against solid malignancies via induction of systemic IL6 in the host.See related commentary by Fiering and Ho, p. 3795.

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