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Curcumin reverses t cell-mediated adaptive immune dysfunctions in tumor-bearing hosts

cellular & Molecular Immunology 2010年第4期7卷 306-315页

作者： Sankar Bhattacharyya Dewan Md Sakib Hossain Suchismita Mohanty Gouri Sankar Sen Sreya Chattopadhyay Shuvomoy Banerjee Juni Chakraborty Kaushik Das Diptendra Sarkar tanya Das Gaurisankar Sa Division of Molecular Medicine Bose InstituteKolkataIndia

Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion.CD81 cytotoxic t lymphocytes(CtLs)are involved in antigen-specific tumor destruction and CD41 t cells are essential for helping this CD81 t cell-dependent tumor eradication.tumors often target and inhibit t-cell function to escape from immune surveillance.this dysfunction includes loss of effector and memory t cells,bias towards type 2 cytokines and expansion of t regulatory(treg)cells.Curcumin has previously been shown to have antitumor activity and some research has addressed the immunoprotective potential of this plant-derived polyphenol in tumor-bearing hosts.Here we examined the role of curcumin in the prevention of tumor-induced dysfunction of t cell-based immune responses.We observed severe loss of both effector and memory t-cell populations,downregulation of type 1 and upregulation of type 2 immune responses and decreased proliferation of effector t cells in the presence of tumors.Curcumin,in turn,prevented this loss of t cells,expanded central memory t cell(tCM)/effector memory t cell(tEM)populations,reversed the type 2 immune bias and attenuated the tumor-induced inhibition of t-cell proliferation in tumor-bearing hosts.Further investigation revealed that tumor burden upregulated treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor(tGF)-b and IL-10 in these cells.Curcumin,however,inhibited the suppressive activity of treg cells by downregulating the production of tGF-b and IL-10 in these cells.More importantly,curcumin treatment enhanced the ability of effector t cells to kill cancer cells.Overall,our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses.

关键词： CD41/CD81 t cell Effector t cell t-regulatory cell FoxP3 th1/th2

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