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A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells

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 im...

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Autores principales: Chatterjee, Shilpak, Mookerjee, Ananda, Mookerjee Basu, Jayati, Chakraborty, Paramita, Ganguly, Avishek, Adhikary, Arghya, Mukhopadhyay, Debanjan, Ganguli, Sudipta, Banerjee, Rajdeep, Ashraf, Mohammad, Biswas, Jaydip, Das, Pradeep K., Sa, Gourisankar, Chatterjee, Mitali, Das, Tanya, Choudhuri, Soumitra Kumar
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737642/
https://www.ncbi.nlm.nih.gov/pubmed/19756150
http://dx.doi.org/10.1371/journal.pone.0007048
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author Chatterjee, Shilpak
Mookerjee, Ananda
Mookerjee Basu, Jayati
Chakraborty, Paramita
Ganguly, Avishek
Adhikary, Arghya
Mukhopadhyay, Debanjan
Ganguli, Sudipta
Banerjee, Rajdeep
Ashraf, Mohammad
Biswas, Jaydip
Das, Pradeep K.
Sa, Gourisankar
Chatterjee, Mitali
Das, Tanya
Choudhuri, Soumitra Kumar
author_facet Chatterjee, Shilpak
Mookerjee, Ananda
Mookerjee Basu, Jayati
Chakraborty, Paramita
Ganguly, Avishek
Adhikary, Arghya
Mukhopadhyay, Debanjan
Ganguli, Sudipta
Banerjee, Rajdeep
Ashraf, Mohammad
Biswas, Jaydip
Das, Pradeep K.
Sa, Gourisankar
Chatterjee, Mitali
Das, Tanya
Choudhuri, Soumitra Kumar
author_sort Chatterjee, Shilpak
collection PubMed
description 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.
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spelling pubmed-27376422009-09-16 A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells Chatterjee, Shilpak Mookerjee, Ananda Mookerjee Basu, Jayati Chakraborty, Paramita Ganguly, Avishek Adhikary, Arghya Mukhopadhyay, Debanjan Ganguli, Sudipta Banerjee, Rajdeep Ashraf, Mohammad Biswas, Jaydip Das, Pradeep K. Sa, Gourisankar Chatterjee, Mitali Das, Tanya Choudhuri, Soumitra Kumar PLoS One Research Article 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. Public Library of Science 2009-09-16 /pmc/articles/PMC2737642/ /pubmed/19756150 http://dx.doi.org/10.1371/journal.pone.0007048 Text en Choudhuri et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chatterjee, Shilpak
Mookerjee, Ananda
Mookerjee Basu, Jayati
Chakraborty, Paramita
Ganguly, Avishek
Adhikary, Arghya
Mukhopadhyay, Debanjan
Ganguli, Sudipta
Banerjee, Rajdeep
Ashraf, Mohammad
Biswas, Jaydip
Das, Pradeep K.
Sa, Gourisankar
Chatterjee, Mitali
Das, Tanya
Choudhuri, Soumitra Kumar
A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells
title A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells
title_full A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells
title_fullStr A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells
title_full_unstemmed A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells
title_short A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells
title_sort novel copper chelate modulates tumor associated macrophages to promote anti-tumor response of t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737642/
https://www.ncbi.nlm.nih.gov/pubmed/19756150
http://dx.doi.org/10.1371/journal.pone.0007048
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