Research Papers: Gerotarget (Focus on Aging):

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

Afshin Beheshti, Justin Wage, J. Tyson McDonald, Clare Lamont, Michael Peluso, Philip Hahnfeldt and Lynn Hlatky _

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Oncotarget. 2015; 6:35419-35432. https://doi.org/10.18632/oncotarget.6214

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Afshin Beheshti1,2, Justin Wage2, J. Tyson McDonald3, Clare Lamont2, Michael Peluso2, Philip Hahnfeldt2 and Lynn Hlatky2

1 Division of Hematology/Oncology, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA

2 Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA, USA

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

Correspondence to:

Lynn Hlatky, email:

Keywords: aging and cancer, tumor progression, tumor microenvironment, CD2, CD3e, Gerotarget

Received: September 22, 2015 Accepted: September 29, 2015 Published: October 21, 2015


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.

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