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Compréhension des mécanismes de l’immunosuppression dans le cancer colorectal .
Nous nous intéressons au microenvironnement immun des tumeurs (primaires et métastases) dans le contexte du cancer colorectal (CRC). Nous étudions en particulier la réponse immunosuppressive se mettant en place lors du CRC. Nous caractérisons l’infiltration immunitaire du microenvironnement tumoral lors du CRC. Cette caractérisation nous permet d’établir le rôle des cellules immunosuppressives telles que les lymphocytes T régulateurs, les macrophages ou encore les cellules suppressives dérivant des myéloïdes (MDSC), dans les CRC. Par ailleurs, nous nous intéressons également au potentiel dialogue immunosuppresseur pouvant exister entre une tumeur primaire colorectale et ses métastases associées. Nous cherchons à comprendre si des signaux, envoyés par une tumeur colorectale, peuvent influencer et polariser le microenvironnement immun des métastases distantes.
Deciphering immunosuppression in colorectal cancer
We are interested in tumor immune microenvironment (composing primary tumors and metastases) in colorectal cancer context. We are exploring in particular the immunosuppressive response occurring during CRC. We are characterizing immune infiltration in CRC tumoral microenvironment. This lead to a detailed characterization of immunosuppressive cells role in CRC, such as lymphocytes, macrophages and/or myeloid-dervied suppressor cells (MDSC). Furthermore, we are interested in the potential cross-talk existing between primary colorectal tumor and associated metastases. We aim to understand if signals (send from a primary colorectal tumor) could influence and polarize distant metastases immune microenvironment.
Nous nous intéressons au microenvironnement immun des tumeurs (primaires et métastases) dans le contexte du cancer colorectal (CRC). Nous étudions en particulier la réponse immunosuppressive se mettant en place lors du CRC. Nous caractérisons l’infiltration immunitaire du microenvironnement tumoral lors du CRC. Cette caractérisation nous permet d’établir le rôle des cellules immunosuppressives telles que les lymphocytes T régulateurs, les macrophages ou encore les cellules suppressives dérivant des myéloïdes (MDSC), dans les CRC. Par ailleurs, nous nous intéressons également au potentiel dialogue immunosuppresseur pouvant exister entre une tumeur primaire colorectale et ses métastases associées. Nous cherchons à comprendre si des signaux, envoyés par une tumeur colorectale, peuvent influencer et polariser le microenvironnement immun des métastases distantes.
Deciphering immunosuppression in colorectal cancer
We are interested in tumor immune microenvironment (composing primary tumors and metastases) in colorectal cancer context. We are exploring in particular the immunosuppressive response occurring during CRC. We are characterizing immune infiltration in CRC tumoral microenvironment. This lead to a detailed characterization of immunosuppressive cells role in CRC, such as lymphocytes, macrophages and/or myeloid-dervied suppressor cells (MDSC). Furthermore, we are interested in the potential cross-talk existing between primary colorectal tumor and associated metastases. We aim to understand if signals (send from a primary colorectal tumor) could influence and polarize distant metastases immune microenvironment.
Production scientifique scientific production
-Yong CS, John LB, Devaud C, Prince MH, Johnstone RW, Trapani JA, Darcy PK, Kershaw MH. A role for multiple chimeric antigen receptor-expressing leukocytes in antigen-specific responses to cancer. Oncotarget. 2016 May 2 [Epub ahead of print]
-Yong CSM, Westwood JA, Schroeder J, Papenfuss A, Moeller M, Adams J, Dardalhon V, Taylor N, Devaud C , Darcy PK, Kershaw MH. A chimeric antigen receptor is expressed in multiple leukocyte lineages in transgenic mice under the control of the vav promoter. PLoS One 2015 Oct 27;10(10):e0140543
-Devaud C, John LB, Westwood JA, Yong CSM, Beavis P, Darcy PK, Kershaw MH. Cross-talk between tumors can affect responses to therapy. OncoImmunology, 2015 Jun 17; 4(7).
-Devaud C, Westwood JA, Teng M, John LB, Yong CSM, Duong CP, Smyth MJ, Darcy PK, Kershaw MH. Differential potency of regulatory T cell-mediated immunosuppression in kidney tumors compared to subcutaneous tumors. OncoImmunology, 2014 Dec 21; (3)11.
-Devaud C, Yong CS, John LB, Westwood JA, Duong CP, House CM, Denoyer D, Li J, Darcy PK, Kershaw MH. Foxp3 expression in macrophages associated with RENCA tumors in mice. PLoS One. 2014 Sep 29; (9).
-Devaud C, Darcy PK, Kershaw MH. Foxp3 expression in T regulatory cells and other cell lineages. Cancer Immunology, Immunotherapy, 2014 Sep 63; (9) 869-76.
-Devaud C, Westwood JA, John LB, Flynn JK, Paquet-Fifield S, Duong CPM, Yong CSM, Achen MG, Stewart TJ, Snyder SA, Smyth MJ, Darcy PK, Kershaw MH. Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy. Mol Ther, 2014 Jan; 22(1):18-27.
-John L. B, Devaud C, Duong CP, Yong CS, Beavis PA, Haynes NM, Chow MT, Smyth MJ, Kershaw MH, Darcy PK. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Can Res, 2013 Oct 15, 19(20); 5636-46.
-Beavis PA, Divisekera U, Paget C, Chow MT, John LB, Devaud C, Dwyer K, Stagg J, Smyth MJ, Darcy PK, Blockade of either A2A or A2B receptors potently suppresses the metastasis of CD73+ tumors. PNAS. 2013. 3,
-Kershaw MH, Devaud C, John LB, Westwood JA, Darcy PK. Enhancing immunotherapy using chemotherapy and radiation to modify the tumor microenvironment. Oncoimmunology. 2013 Sep 1; 2(9):e25962.
-Devaud C, John LB, Westwood JA, Darcy PK, Kershaw MH. Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy, OncoImmunology, 2013 Aug 1; 2(8):e25961.
-Devaud C, Rousseau B, Netzer S, Pitard V, Paroissin C, Costet P, Moreau JF, Couillaud F, Dechanet-Merville J, Capone M. Anti-metastatic potential of human Vδ1+ γδ T cells in an orthotopic mouse xenograft model of colon carcinoma. Canc Immunol Immunoth, 2013 Jul, 62(7):1199-210.
-Henderson MS, Yong CSM, Duong CPM, Davenport AJ, John LB, Devaud C, Neeson P, Westwood JA, Darcy PK, Kershaw MJ. Chimeric antigen receptor-redirected T cells display multifunctional capacity and enhanced tumor-specific cytokine secretion upon secondary ligation of chimeric receptor. Immunotherapy. 2013. 5(6):577-90.
-Duong CPM, Westwood JA, Yong CSM, Murphy A, Devaud C, John LB, Darcy PK, Kershaw MH. Engineering T cell function using chimeric antigen receptors identified using a DNA library approach. PloS One. 2013. 7; 8(5):e63037.
-Daburon S, Devaud C, Costet P, Morello A, Garrigue-Antar L, Maillasson M, Hargous N, Lapaillerie D, Bonneu M, Dechanet-Merville J, Legembre P, Capone M, Moreau JF, Taupin JL. Functional characterization of a chimeric soluble FasL polymer with in vivo anti-tumor activity. PloS One. 2013; 8(1), e54000.
-Yong CSM, Duong CPM, Devaud C, John LB, Darcy PK, Kershaw MK. Using electroporation to determine function of a chimeric antigen receptor in T cells and macrophage cell lines. The Open Gene Therapy Journal, 2013, 5, 1-11. 1. 1875-0370/13.
-John LB, Howland LJ, Flynn JK, West AC, Devaud C, Duong CPM, Stewart TJ, Westwood JA, Guo ZS, Bartlett DL, Smyth MJ, Kershaw MH, Darcy PK. Oncolytic virus and 4-1BB combination therapy elicits strong anti-tumor immunity against established cancer. Canc Res. 2012. 1; 72(7):1651-60.
-Devaud C, Bilhere E, Loizon S, Pitard V, Behr C, Moreau JF, Dechanet-Merville J, Capone M. Anti-tumor activity of cytomegalovirus-induced Vδ2neg γδ T cells in a mouse tumor xenograft model. Canc Res, 2009; 69: (9).
-Yong CSM, Westwood JA, Schroeder J, Papenfuss A, Moeller M, Adams J, Dardalhon V, Taylor N, Devaud C , Darcy PK, Kershaw MH. A chimeric antigen receptor is expressed in multiple leukocyte lineages in transgenic mice under the control of the vav promoter. PLoS One 2015 Oct 27;10(10):e0140543
-Devaud C, John LB, Westwood JA, Yong CSM, Beavis P, Darcy PK, Kershaw MH. Cross-talk between tumors can affect responses to therapy. OncoImmunology, 2015 Jun 17; 4(7).
-Devaud C, Westwood JA, Teng M, John LB, Yong CSM, Duong CP, Smyth MJ, Darcy PK, Kershaw MH. Differential potency of regulatory T cell-mediated immunosuppression in kidney tumors compared to subcutaneous tumors. OncoImmunology, 2014 Dec 21; (3)11.
-Devaud C, Yong CS, John LB, Westwood JA, Duong CP, House CM, Denoyer D, Li J, Darcy PK, Kershaw MH. Foxp3 expression in macrophages associated with RENCA tumors in mice. PLoS One. 2014 Sep 29; (9).
-Devaud C, Darcy PK, Kershaw MH. Foxp3 expression in T regulatory cells and other cell lineages. Cancer Immunology, Immunotherapy, 2014 Sep 63; (9) 869-76.
-Devaud C, Westwood JA, John LB, Flynn JK, Paquet-Fifield S, Duong CPM, Yong CSM, Achen MG, Stewart TJ, Snyder SA, Smyth MJ, Darcy PK, Kershaw MH. Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy. Mol Ther, 2014 Jan; 22(1):18-27.
-John L. B, Devaud C, Duong CP, Yong CS, Beavis PA, Haynes NM, Chow MT, Smyth MJ, Kershaw MH, Darcy PK. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Can Res, 2013 Oct 15, 19(20); 5636-46.
-Beavis PA, Divisekera U, Paget C, Chow MT, John LB, Devaud C, Dwyer K, Stagg J, Smyth MJ, Darcy PK, Blockade of either A2A or A2B receptors potently suppresses the metastasis of CD73+ tumors. PNAS. 2013. 3,
-Kershaw MH, Devaud C, John LB, Westwood JA, Darcy PK. Enhancing immunotherapy using chemotherapy and radiation to modify the tumor microenvironment. Oncoimmunology. 2013 Sep 1; 2(9):e25962.
-Devaud C, John LB, Westwood JA, Darcy PK, Kershaw MH. Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy, OncoImmunology, 2013 Aug 1; 2(8):e25961.
-Devaud C, Rousseau B, Netzer S, Pitard V, Paroissin C, Costet P, Moreau JF, Couillaud F, Dechanet-Merville J, Capone M. Anti-metastatic potential of human Vδ1+ γδ T cells in an orthotopic mouse xenograft model of colon carcinoma. Canc Immunol Immunoth, 2013 Jul, 62(7):1199-210.
-Henderson MS, Yong CSM, Duong CPM, Davenport AJ, John LB, Devaud C, Neeson P, Westwood JA, Darcy PK, Kershaw MJ. Chimeric antigen receptor-redirected T cells display multifunctional capacity and enhanced tumor-specific cytokine secretion upon secondary ligation of chimeric receptor. Immunotherapy. 2013. 5(6):577-90.
-Duong CPM, Westwood JA, Yong CSM, Murphy A, Devaud C, John LB, Darcy PK, Kershaw MH. Engineering T cell function using chimeric antigen receptors identified using a DNA library approach. PloS One. 2013. 7; 8(5):e63037.
-Daburon S, Devaud C, Costet P, Morello A, Garrigue-Antar L, Maillasson M, Hargous N, Lapaillerie D, Bonneu M, Dechanet-Merville J, Legembre P, Capone M, Moreau JF, Taupin JL. Functional characterization of a chimeric soluble FasL polymer with in vivo anti-tumor activity. PloS One. 2013; 8(1), e54000.
-Yong CSM, Duong CPM, Devaud C, John LB, Darcy PK, Kershaw MK. Using electroporation to determine function of a chimeric antigen receptor in T cells and macrophage cell lines. The Open Gene Therapy Journal, 2013, 5, 1-11. 1. 1875-0370/13.
-John LB, Howland LJ, Flynn JK, West AC, Devaud C, Duong CPM, Stewart TJ, Westwood JA, Guo ZS, Bartlett DL, Smyth MJ, Kershaw MH, Darcy PK. Oncolytic virus and 4-1BB combination therapy elicits strong anti-tumor immunity against established cancer. Canc Res. 2012. 1; 72(7):1651-60.
-Devaud C, Bilhere E, Loizon S, Pitard V, Behr C, Moreau JF, Dechanet-Merville J, Capone M. Anti-tumor activity of cytomegalovirus-induced Vδ2neg γδ T cells in a mouse tumor xenograft model. Canc Res, 2009; 69: (9).