Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development.
The concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3ε, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease.
Division of Hematology/Oncology, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA.|Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA, USA.
Afshin
A
Beheshti
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA, USA.
Justin
J
Wage
Cancer Research Center, Hampton University, Hampton, VA, USA.
J Tyson
JT
McDonald
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA, USA.
Clare
C
Lamont
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA, USA.
Michael
M
Peluso
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA, USA.
Philip
P
Hahnfeldt
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA, USA.
Lynn
L
Hlatky
D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D051379:Mice; D009369:Neoplasms; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment
CD2; CD3e; Gerotarget; aging and cancer; tumor microenvironment; tumor progression