alexa Repeated restraint stress impairs the antitumor T cell response through its suppressive effect on Th1-type CD4+ T cells.
Oncology

Oncology

Journal of Cancer Science & Therapy

Author(s): Li T, Harada M, Tamada K, Abe K, Nomoto K

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Abstract Stressful events suppress a broad spectrum of immunological responses. However, the effects of stress on the antitumor T cell response against syngeneic tumors have not yet been closely studied. In the present study, we investigated the effects of repeated restraint stress on the antitumor T cell response against syngeneic B16 melanoma. The stress, before and after immunization with tumor cells, decreased the potential of the spleen cells to turn into antitumor cytotoxic T lymphocytes (CTLs) after in vitro restimulation. In a cytokine assay, the stress significantly suppressed the tumor-specific CD4+ T cell-dependent IFN-gamma production of immunized spleen cells. The stress also decreased their spontaneous IL-2 production, but it apparently had no effect on IL-4 production. The in vitro addition of IL-2, however, restored the stress-induced inability of the spleen cells to turn into antitumor CTLs after in vitro restimulation, thus suggesting that stress has no definite effect on tumor-specific CD8+ T cells. Stress had no effect on the natural killer (NK) activity of the spleen cells, but did decrease their responsiveness to poly (I:C), an NK activity augmentator. In addition, stress did not influence primary tumor growth but did decrease the degree of protective immunity at rechallenge. On the other hand, stress elevated the serum level of corticosterone and, in addition, the in vivo administration of dexamethasone, a synthetic glucocorticoid, decreased the capacity of the immunized spleen cells to turn into antitumor CTLs after in vitro restimulation and to produce both IFN-gamma and IL-2 in a manner similar to that of mice burdened by stress. Moreover, stress decreased the potential of spleen cells to produce both IFN-gamma and IL-2 in response to anti-CD3 mAb. Overall, these findings provide evidence that stress significantly impairs the antitumor T cell responses through its suppressive effect on Th1-type CD4+ T cells.
This article was published in Anticancer Res and referenced in Journal of Cancer Science & Therapy

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