Oncotarget

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, Lynn Hlatky _

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

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Abstract

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

Abstract

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.

Author Information

Afshin Beheshti

Justin Wage

J. Tyson McDonald

Clare Lamont

Michael Peluso

Philip Hahnfeldt

Lynn Hlatky
Primary Contact  _


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