Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity

Shamgar Ben-Eliyahu, Gayle G. Page, Raz Yirmiya, Guy Shakhar

Research output: Contribution to journalArticlepeer-review

Abstract

Stress and surgery have been suggested to compromise host resistance to infectious and malignant diseases in experimental and clinical settings. Because stress affects numerous physiological systems, the role of the immune system in mediating such effects is unclear. In the current study, we assessed the degree to which stress-induced alterations in natural killer (NK) cell activity underlie increased susceptibility to tumor development in F344 rats. Two stress paradigms were used: forced swim and abdominal surgery. Host resistance to tumor development was studied using 3 tumor models syngeneic to inbred F344 rats: CRNK-16 leukemia and the MADB106 mammary adenocarcinoma, both sensitive to NK activity, and the NK-insensitive C4047 colon cancer. Swim stress increased CRNK-16-associated mortality and metastatic development of MADB106 but not metastasis of C4047 cells. In both stress paradigms, stress suppressed NK activity (NKA) for a duration that paralleled its metastasis-enhancing effects on the MADB 106 tumor. In vivo depletion of large granular lymphocyte/NK cells abolished the metastasis- enhancing effects of swim stress but not of surgical stress. Our findings indicate that stress-induced suppression of NKA is sufficient to cause enhanced tumor development. Under certain stressful conditions, suppression of NKA is the primary mediator of the tumor-enhancing effects of stress, while under other conditions, additional factors play a significant role. Clinical circumstances in which surgical stress may induce enhanced metastatic growth are discussed.

Original languageEnglish (US)
Pages (from-to)880-888
Number of pages9
JournalInternational Journal of Cancer
Volume80
Issue number6
DOIs
StatePublished - Mar 15 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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