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Environmental Enrichment Augments the Efficacy of Idiotype Vaccination for B-cell Lymphoma

Benaroya-Milshtein, Noa* †; Apter, Alan; Yaniv, Isaac; Kukulansky, Tova§; Raz, Nava§; Haberman, Yael*; Halpert, Hila*; Pick, Chaim G.*; Hollander, Nurit§

doi: 10.1097/CJI.0b013e31804efc5e
Basic Studies

Environmental enrichment is known to positively influence the organism's psychologic and physiologic well-being. However, the effects of environmental enrichment on immune responses and cancer prognosis have not been clearly established and its impact on cancer therapy is unknown. Here, we report that environmental enrichment mediated a statistically significant improvement of the outcome of immunotherapy in an experimental model of B-cell lymphoma. When mice were immunized with an idiotype-vaccine, those maintained under enriched environmental conditions produced statistically significant higher levels of anti-idiotype antibodies and revealed more attenuated tumor growth than those housed in standard environments. Most strikingly, enriched tumor-bearing mice had statistically significant prolonged survival, with 44% of them disease-free compared with 0% in the standard rearing tumor-bearing mice. The possible mechanisms for the enhancement of immunotherapy by environmental enrichment are cognitive, physical activity, and psychologic. The demonstration of synergistic effect of cancer therapy and environmental enrichment on tumor rejection has important implication for cancer treatment.

Departments of *Anatomy

§Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel

Departments of Psychiatry

Hemato-Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Israel

Financial disclosure: the authors declare there are no financial conflicts of interest in regard to this work.

Sources of support that require acknowledgment: (1) Israel Science Foundation grant 635/02 (N.H.). (2) “Oncology Memorial Fund,” Israel, this research has won an award as part of a psycho-oncology project on “The effects of psychological interventions on cancer course; animals and human models.”

Noa Benaroya-Milshtein is enrolled in the MD/PhD excellence program of the Sackler Faculty of Medicine, Tel Aviv University, Israel. This work was performed in partial fulfillment of the requirements for her PhD thesis. Chaim G. Pick and Nurit Hollander share senior authorship.

Reprints: Chaim G. Pick, Department of Anatomy, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel (e-mail:

Received for publication June 13, 2006; accepted December 5, 2006

© 2007 Lippincott Williams & Wilkins, Inc.