Simulated microgravity-mediated reversion of murine lymphoma immune evasion

• Published in: Scientific reports Vol. 9; no. 1; pp. 14623 - 11
• Main Authors: Bradley, Jillian H., Barwick, Shannon, Horn, Gillian Q., Ullrich, Elizabeth, Best, Brianna, Arnold, Jennifer P., Gregg, Randal K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-10-2019; Nature Publishing Group
• Subjects: 13/106; 13/2; 13/21; 13/31; 14/63; 631/250/1619/554/1834/1269; 631/250/1619/554/1898/1272; 631/250/2161; 631/250/580/1884/2323; 631/67/1990/291/1621/1916; 64/60; 82/80; Animals; Cancer; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell culture; Cell Culture Techniques - methods; Cell Line, Tumor; Cell Proliferation; Coculture Techniques; Cosmic Radiation - adverse effects; Dendritic cells; Humanities and Social Sciences; Humans; Immune evasion; Lymphocytes; Lymphocytes T; Lymphoma; Lymphoma - immunology; Lymphoma - pathology; Lymphoma - therapy; Mice; Microgravity; Moon; multidisciplinary; Science; Science (multidisciplinary); Space Flight; Tumor cells; Tumor Escape - immunology; Weightlessness Simulation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-51106-y

No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and protective biologicals are under development, little is known concerning the interaction between cancer cells and host immunity in microgravity. As a hallmark of cancer, tumor cells employ mechanisms of immune evasion to avoid elimination by protective CD4
+
and CD8
+
T cells. We showed that a murine lymphoma was able to produce a soluble factor that inhibited the function of dendritic cells in activating the CD4
+
T cells. Culture of the lymphoma cells in simulated microgravity (SMG), and not Static conditions, restored the CD4
+
T cell response and augmented CD8
+
T cell-mediated destruction of the cancer cells
in vitro
and
in vivo
. Thus, SMG impaired the mechanism of tumor escape and rendered the cancer cells more susceptible to T cell-mediated elimination. The stress of microgravity may expose the most critical components of a tumor’s escape mechanism for astronaut protection and the generation of new cancer therapeutics for patients on Earth.