Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy

Devaud, Christel, Westwood, Jennifer A., John, Liza B., Flynn, Jacqueline K., Paquet-Fifield, Sophie, Duong, Connie P. M., Yong, Carmen S. M., Pegram, Hollie J., Stacker, Steven A., Achen, Marc G., Stewart, Trina J., Snyder, Linda A., Teng, Michele W. L., Smyth, Mark J., Darcy, Phillip K. and Kershaw, Michael H. (2014) Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy. Molecular Therapy, 22 1: 18-27. doi:10.1038/mt.2013.219

Author Devaud, Christel
Westwood, Jennifer A.
John, Liza B.
Flynn, Jacqueline K.
Paquet-Fifield, Sophie
Duong, Connie P. M.
Yong, Carmen S. M.
Pegram, Hollie J.
Stacker, Steven A.
Achen, Marc G.
Stewart, Trina J.
Snyder, Linda A.
Teng, Michele W. L.
Smyth, Mark J.
Darcy, Phillip K.
Kershaw, Michael H.
Title Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy
Journal name Molecular Therapy   Check publisher's open access policy
ISSN 1525-0016
Publication date 2014-01-01
Sub-type Article (original research)
DOI 10.1038/mt.2013.219
Open Access Status DOI
Volume 22
Issue 1
Start page 18
End page 27
Total pages 10
Place of publication London, England, U.K.
Publisher Nature Publishing Group
Language eng
Subject 1312 Molecular Biology
1313 Molecular Medicine
1311 Genetics
3002 Drug Discovery
3004 Pharmacology
Abstract The tumor microenvironment can promote tumor growth and reduce treatment efficacy. Tumors can occur in many sites in the body, but how surrounding normal tissues at different anatomical sites affect tumor microenvironments and their subsequent response to therapy is not known.We demonstrated that tumors from renal, colon, or prostate cell lines in orthotopic locations responded to immunotherapy consisting of three agonist antibodies, termed Tri-mAb, to a much lesser extent than the same tumor type located subcutaneously. A tissue-specific response to Tri-mAb was confirmed by ex vivo separation of subcutaneous (SC) or orthotopic tumor cells from stromal cells, followed by reinjection of tumor cells into the opposite site. Compared with SC tumors, orthotopic tumors had a microenvironment associated with a type 2 immune response, related to immunosuppression, and an involvement of alternatively activated macrophages in the kidney model. Orthotopic kidney tumors were more highly vascularized than SC tumors. Neutralizing the macrophage- and Th2-associated molecules chemokine (C-C motif) ligand 2 or interleukin-13 led to a significantly improved therapeutic effect. This study highlights the importance of the tissue of implantation in sculpting the tumor microenvironment. These are important fundamental issues in tumor biology and crucial factors to consider in the design of experimental models and treatment strategies.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Created: Wed, 01 Apr 2015, 08:29:50 EST by Matthew Lamb on behalf of School of Medicine