A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T CellsReportar como inadecuado




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Background

At the early stages of carcinogenesis, the induction of tumor specific T cell mediated immunity seems to block the tumor growth and give protective anti-tumor immune response. However, tumor associated macrophages TAMs might play an immunosuppressive role and subvert this anti tumor immunity leading to tumor progression and metastasis.

Methodology-Principal Findings

The Cu II complex, chelate, copper N-2-hydroxy acetophenone glycinate CuNG, synthesized by us, has previously been shown to have a potential usefulness in immunotherapy of multiple drug resistant cancers. The current study demonstrates that CuNG treatment of TAMs modulates their status from immunosuppressive to proimmunogenic nature. Interestingly, these activated TAMs produced high levels of IL-12 along with low levels of IL-10 that not only allowed strong Th1 response marked by generation of high levels of IFN-γ but also reduced activation induced T cell death. Similarly, CuNG treatment of peripheral blood monocytes from chemotherapy and-or radiotherapy refractory cancer patients also modulated their cytokine status. Most intriguingly, CuNG treated TAMs could influence reprogramming of TGF-β producing CD4+CD25+ T cells toward IFN-γ producing T cells.

Conclusion-Significance

Our results show the potential usefulness of CuNG in immunotherapy of drug-resistant cancers through reprogramming of TAMs that in turn reprogram the T cells and reeducate the T helper function to elicit proper anti-tumorogenic Th1 response leading to effective reduction in tumor growth.



Autor: Shilpak Chatterjee , Ananda Mookerjee , Jayati Mookerjee Basu , Paramita Chakraborty, Avishek Ganguly, Arghya Adhikary, Debanjan

Fuente: http://plos.srce.hr/



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