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Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer
Open accessAbstract
Aerobic exercise is associated with decreased cancer incidence and cancer-associated mortality. However, little is known about the effects of exercise on pancreatic ductal adenocarcinoma (PDA), a disease for which current therapeutic options are limited. Herein, we show that aerobic exercise reduces PDA tumor growth, by modulating systemic and intra-tumoral immunity. Mechanistically, exercise promotes immune mobilization and accumulation of tumor-infiltrating IL15Rα+ CD8 T cells, which are responsible for the tumor-protective effects. In clinical samples, an exercise-dependent increase of intra-tumoral CD8 T cells is also observed. Underscoring the translational potential of the interleukin (IL)-15/IL-15Rα axis, IL-15 super-agonist (NIZ985) treatment attenuates tumor growth, prolongs survival, and enhances sensitivity to chemotherapy. Finally, exercise or NIZ985 both sensitize pancreatic tumors to αPD-1, with improved anti-tumor and survival benefits. Collectively, our findings highlight the therapeutic potential of an exercise-oncology axis and identify IL-15 activation as a promising treatment strategy for this deadly disease.
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“Exercise restrains tumor growth5 and enhances immune checkpoint inhibitor (ICI) efficacy in various preclinical cancer models8–13”
From Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy (2025) · cites this paper as [8]
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“Exercise exerts potent antitumor effects in both preclinical models5,8–13 and cancer patients6.”
From Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy (2025) · cites this paper as [8]
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Metadata
- Authors
- Kurz, E., Hirsch, C. A., Dalton, T., Shadaloey, S. A., Khodadadi-Jamayran, A., Miller, G., Pareek, S., Rajaei, H., Mohindroo, C., Baydogan, S., Ngo-Huang, A., Parker, N., Katz, M. H. G., Petzel, M., Vucic, E., McAllister, F., Schadler, K., Winograd, R., & Bar-Sagi, D.
- Affiliations
- New York University (US)
- Columbia University Irving Medical Center (US)
- Trinity Health (US)
- The University of Texas MD Anderson Cancer Center (US)
- Moffitt Cancer Center (US)
- NYU Langone Health (US)
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 40
- Issue
- 7
- Pages
- 720-737.e5
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC9280705
- OpenAlex
- W4282010758
- Cited by
- 258
- References
- 81
- Citations by year
- 2026: 58 · 2025: 69 · 2024: 62 · 2023: 48 · 2022: 21
- FWCI
- 21.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 375 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas (RP200173)
- National Institutes of Health (CA210263, T32- GM136573, T32CA193111, F30 CA243205)
- Novartis
- National Center for Advancing Translational Sciences
- Stanford Genome Technology Center
- Green Templeton College, University of Oxford
- The University of Texas MD Anderson Cancer Center Duncan Family Institute for Cancer Prevention and Risk Assessment
- National Cancer Institute (/ NCI 5 P30CA16087, S10 OD021747, NIZ985)
- Canadian Institutes of Health Research (146792, R21CA218732, P30CA016672, R37CA237384\u201301A1, RP170259)
- New York University (T32CA193111, F30 CA243205, T32- GM136573)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- aerobic exercise, pancreatic ductal adenocarcinoma, antitumor immunity, CD8+ T cells, tumor-infiltrating lymphocytes, anti-PD-1 therapy, chemosensitivity, exercise oncology
- MeSH terms
- Antineoplastic Agents, Humans, Immunotherapy, Pancreatic Neoplasms, CD8-Positive T-Lymphocytes, Interleukin-15, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Receptors, Interleukin-15, Tumor Microenvironment
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