Journal article
Exercise-induced engagement of the IL-15/1L-15Rα axis promotes anti-tumor immunity in pancreatic cancer
Cancer cell, Vol.40(7), p.720
07/11/2022
DOI: 10.1016/j.ccell.2022.05.006
PMID: 35660135
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 IL15R alpha(+) 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-15R alpha 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 alpha PD-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.
Details
- Title: Subtitle
- Exercise-induced engagement of the IL-15/1L-15Rα axis promotes anti-tumor immunity in pancreatic cancer
- Creators
- Emma Kurz - New York UniversityCarolina Alcantara Hirsch - New York UniversityTanner Dalton - Columbia University Irving Medical CenterSorin Alberto Shadaloey - New York UniversityAlireza Khodadadi-Jamayran - New York UniversityGeorge Miller - Trinity HealthSumedha Pareek - The University of Texas MD Anderson Cancer CenterHajar Rajaei - The University of Texas MD Anderson Cancer CenterChirayu Mohindroo - The University of Texas MD Anderson Cancer CenterSeyda Baydogan - The University of Texas MD Anderson Cancer CenterAn Ngo-Huang - The University of Texas MD Anderson Cancer CenterNathan Parker - Moffitt Cancer CenterMatthew H. G. Katz - The University of Texas MD Anderson Cancer CenterMaria Petzel - Univ Texas MD Anderson Canc Ctr, Dept Clin Nutr, 1515 Holcombe Blvd, Houston, TX 77030 USAEmily Vucic - New York UniversityFlorencia McAllister - The University of Texas MD Anderson Cancer CenterKeri Schadler - The University of Texas MD Anderson Cancer CenterRafael Winograd - NYU Langone HealthDafna Bar-Sagi - New York University
- Resource Type
- Journal article
- Publication Details
- Cancer cell, Vol.40(7), p.720
- DOI
- 10.1016/j.ccell.2022.05.006
- PMID
- 35660135
- NLM abbreviation
- Cancer Cell
- ISSN
- 1535-6108
- eISSN
- 1878-3686
- Publisher
- Elsevier
- Number of pages
- 24
- Grant note
- Duncan Family Institute for Cancer Prevention and Risk Assessment R37CA237384-01A1 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) RP200173 / CPRIT; Cancer Prevention & Research Institute of Texas T32GM136573 / National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) 5 P30CA16087; F30 CA243205; T32-GM136573; R21CA218732; P30CA016672; CA210263 / NIH/NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 146792 / Canadian Institutes of Health Research Fellowship; Canadian Institutes of Health Research (CIHR) Wyck Knox Jr. Family Foundation T32CA193111; R37CA237384; P30CA016672; R35CA210263; F30CA243205; P30CA016087 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) RP170259 / Cancer Prevention & Research Institute of Texas Training Grant/MD Anderson Cancer Prevention Research Training Program; Cancer Prevention & Research Institute of Texas UL1 TR000038 / NCATS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Language
- English
- Date published
- 07/11/2022
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985177932302771
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