IL6 fuels durable memory for Th17 cell–mediated responses to tumors
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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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From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [123]
The Introduction and Discussion discuss shortening T-cell expansion to reduce treatment delays, but neither addresses sterility testing. Searches for the Cell and Gene Therapy Catapult, industry partners, and one-hour sterility testing found no passage supporting the claim in our copy. (LLM, conf=0.78)
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Self-citation
- Authors
- Knochelmann, H. M., Dwyer, C. J., Smith, A. S., Bowers, J. S., Wyatt, M. M., Nelson, M. H., Rangel Rivera, G. O., Horton, J. D., Krieg, C., Armeson, K., Lesinski, G. B., Rubinstein, M. P., Li, Z., & Paulos, C. M.
- Affiliations
- Medical University of South Carolina (US)
- 1Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, South Carolina.
- Winship Cancer Institute (US)
- The Ohio State University (US)
- Corresponding author
- Knochelmann, Hannah M.
- Paulos, Chrystal M.
- ORCID
- Venue
- Cancer Research
- Published
- 2020-09-15
- Volume
- 80
- Issue
- 18
- Pages
- 3920-3932
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC7501223
- OpenAlex
- W3035839813
- Cited by
- 37
- References
- 47
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 2
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NCI (F30 CA243307, R01 CA222817, R01 CA175061, R01 CA208514, P30 CA138313)
- NIH (T32 GM008716, DE017551, T32 AI132164-01, T32 DE017551, F30 CA200272, R50 CA233186)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- Th17 cells, adoptive T cell therapy, interleukin-6, ex vivo T cell expansion, antitumor immunity, memory T cells, Foxp3+ regulatory T cells, solid tumors, IL-17, MCP-1, GM-CSF, T cell engraftment
- MeSH terms
- Humans, Neoplasms, Interleukin-6, Cytokines, Th17 Cells, Cell- and Tissue-Based Therapy
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