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The Impact of Simulated Microgravity on the Anti-Tumor Properties of Human NK-Cells and T Cells In Vivo: IL-2 and Zoledronic Acid Therapy as a Potential Countermeasure (80NSSC19K1059)
Research Area:
Cellular and molecular biology
Species Studied
Scientific Name: Species: Cells, human
Scientific Name: Mus musculus Species: Mouse

Long-duration space flight and microgravity have been shown to have negative impacts on immune function. Impaired immune function, along with radiation exposure from galactic cosmic rays (GCR) and solar particle events (SPE), has the potential to increase risks for latent viral reactivation and various forms of cancer during exploration missions. Natural Killer (NK)-cells are a critical component of the immune system and play a vital role in detection and regulation of virus-infected cells. Additionally, T-cell receptor (TCR) T cells are a critical component in both anti-tumor and anti-viral surveillance.

Impairments in NK-cell and T cell function during space travel could adversely affect immune surveillance against cancer and viruses at a time when crewmembers are exposed to environmental factors that promote latent viral reactivation and possibly tumor formation. In addition to studying the effects of simulated microgravity on immune dysfunction, preliminary research shows that zoledronic acid (ZOL) in combination with Interleukin-2 (IL-2) to be a potential countermeasure to NK-cell and T cell impairment. IL-2 has been shown to augment NK-cell cytotoxicity by increasing activation, perforin-binding and proliferation. This increase in NK-cell function might override the suppression of function induced by microgravity. Similarly, ZOL has been shown to augment T cell function and proliferation.

Reduced immunity in NK-cell function has been observed in ISS crewmembers on their first mission on the station, and in vitro tests using a rotary cell culture system to replicate microgravity has demonstrated impaired ability of NK-cells to regulate tumor cells in as little as 12 hours in this microgravity analog. Because T cells have emerged as key players in both anti-tumor and anti-viral immune surveillance, this experiment will observe their behavior in vivo, along with NK-cell function, in simulated microgravity.

This study has the following specific aims:

  1. Determine the effect of simulated microgravity (SMG) on the anti-tumor capacity of human NK-cells and ?d-T cells in vivo.
  2. Determine the effect of systemic administration of IL-2 and ZOL on the function of NK and T cells.

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Mylabathula PL, Li L, Bigley AB, Markofski MM, Crucian BE, Mehta SK, Pierson DL, Laughlin MS, Rezvani K, Simpson RJ. Simulated microgravity disarms human NK-cells and inhibits anti-tumor cytotoxicity in vitro. Acta Astronaut. 2020 Sep;174:32-40. [DOI]

Solar activity
Killer cells, natural
Models, biological

Data Information
Data Availability
Archiving in progress. Data is not yet available for this experiment.

Luciferase activity
NK cell function
Tumor formation

Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

Human Research Program (HRP) Human Research Roadmap (HRR) Information
Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) investigates and mitigates the highest risks to human health and performance, providing essential countermeasures and technologies for human space exploration. Risks include physiological and performance effects from hazards such as radiation, altered gravity, and hostile environments, as well as unique challenges in medical support, human factors, and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify the approach and research activities planned to address these risks, which are assigned to specific Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.

The Human Research Roadmap is located at:

+ Click here for information of how this experiment is contributing to the HRP's path for risk reduction.

Additional Information
Managing NASA Center
Johnson Space Center (JSC)
Responsible NASA Representative
Johnson Space Center LSDA Office
Project Manager: Pamela A. Bieri
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
Proposal Source
2017 HERO 80JSC017N0001-Crew Health and Performance