Journal article
Tissues in different anatomical sites can sculpt and vary the tumor microenvironment to affect responses to therapy
C Devaud, JA Westwood, LB John, JK Flynn, S Paquet-Fifield, CPM Duong, CSM Yong, HJ Pegram, SA Stacker, MG Achen, TJ Stewart, LA Snyder, MWL Teng, MJ Smyth, PK Darcy, MH Kershaw
Molecular Therapy | Published : 2014
DOI: 10.1038/mt.2013.219
Open access
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..
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Grants
Awarded by Cancer Council Victoria
Funding Acknowledgements
This work was supported by a grant from the Cancer Council of Victoria, Australia, No. 1006209. M.H.K. and P.K.D. were supported by Senior Research Fellowships from the National Health and Medical Research Council of Australia. The authors thank Viki Milovac and Sophie Curcio of the Peter MacCallum Cancer Center Flow Cytometry Facility for their excellent technical assistance in this study; members of the Peter MacCallum Cancer Center Animal Facility for their care and maintenance of mice used in this study; and Dr Pavel Lobachevsky for his help with the radiolabeled antibody studies. L.A.S. is employed by Janssen Research and Development who supplied the monoclonal anti-CCL2 antibody for this study.