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

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


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.

Keywords: CD2; CD3e; Gerotarget; aging and cancer; tumor microenvironment; tumor progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Cell Proliferation
  • Disease Progression
  • Humans
  • Mice
  • Neoplasms
  • Signal Transduction
  • Spleen / immunology*
  • Spleen / pathology
  • Tumor Microenvironment