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Oncotarget. 2015 Nov 3;6(34):35419-32. doi: 10.18632/oncotarget.6214.

Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development.

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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.
Cancer Research Center, Hampton University, Hampton, VA, USA.


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.


CD2; CD3e; Gerotarget; aging and cancer; tumor microenvironment; tumor progression

[Indexed for MEDLINE]
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