Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts |
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Authors: | 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 |
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Affiliation: | Division of Molecular Medicine, Bose Institute, Kolkata, India |
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Abstract: | Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion. CD8+ cytotoxic T lymphocytes (CTLs) are involved in antigen-specific tumor destruction and CD4+ T cells are essential for helping this CD8+ 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)-β and IL-10 in these cells. Curcumin, however, inhibited the suppressive activity of Treg cells by downregulating the production of TGF-β 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. |
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Keywords: | CD4+ /CD8+ T cell, Effector T cell, T-regulatory cell, FoxP3, Th1/Th2 |
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