Cited by 262Cancer Immunotherapy and BiomarkersPancreatic and Hepatic Oncology ResearchExercise and Physiological Responses

Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer

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Kurz, Emma, Hirsch, Carolina Alcantara, Dalton, Tanner, Shadaloey, Sorin Alberto, Khodadadi-Jamayran, Alireza, Miller, George, Pareek, Sumedha, Rajaei, Hajar +11 more·2022·Cancer Cell

Abstract

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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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)
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2022-07
Volume
40
Issue
7
Pages
720-737.e5
ISSN
1535-6108 (ISSN-L)
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
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 › Rehabilitation › 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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