TY - JOUR
T1 - CD4+ T Cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation
AU - Rakhra, Kavya
AU - Bachireddy, Pavan
AU - Zabuawala, Tahera
AU - Zeiser, Robert
AU - Xu, Liwen
AU - Kopelman, Andrew
AU - Fan, Alice C.
AU - Yang, Qiwei
AU - Braunstein, Lior
AU - Crosby, Erika
AU - Ryeom, Sandra
AU - Felsher, Dean W.
N1 - Funding Information:
This manuscript is dedicated to the memory of Julie Do. We thank Ron Levy, Mina Bissell, Kwan Hyuck, Lisa Coussens, Peter Choi, and other members of the Felsher laboratory for their helpful suggestions; Robert Negrin, Lisa Coussens, and Ben Barres for providing transgenic mice; Pauline Chu for generating histology samples; Anet James for assistance with microscopy; Yael Resenberg-Hasson for assistance with the luminex cytokine assay. This work was funded by the Burroughs Welcome Fund Career Award, the Damon Runyon Foundation Lilly Clinical Investigator Award, NIH RO1 grant number CA 089305, 105102, National Cancer Institute's In-vivo Cellular and Molecular Imaging Center grant number CA 114747, Integrative Cancer Biology Program grant number CA 112973, NIH/NCI PO1 grant number CA034233, the Leukaemia and Lymphoma Society Translational Research grant number R6223-07 (D.W.F.), NIH R01 grant number CA 118374 (S.R.), Stanford Graduate Fellowship (K.R.) Lymphoma Research Foundation and the Leukemia and Lymphoma Society (A.C.F.). Additionally, P.B. and A.K. were funded by a Howard Hughes Medical Institute Research Training Fellowship for Medical Students and a Stanford Medical Scholars Research Fellowship.
PY - 2010/11/16
Y1 - 2010/11/16
N2 - Oncogene addiction is thought to occur cell autonomously. Immune effectors are implicated in the initiation and restraint of tumorigenesis, but their role in oncogene inactivation-mediated tumor regression is unclear. Here, we show that an intact immune system, specifically CD4+ T cells, is required for the induction of cellular senescence, shutdown of angiogenesis, and chemokine expression resulting in sustained tumor regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T cell acute lymphoblastic lymphoma and pro-B cell leukemia, respectively. Moreover, immune effectors knocked out for thrombospondins failed to induce sustained tumor regression. Hence, CD4+ T cells are required for the remodeling of the tumor microenvironment through the expression of chemokines, such as thrombospondins, in order to elicit oncogene addiction.
AB - Oncogene addiction is thought to occur cell autonomously. Immune effectors are implicated in the initiation and restraint of tumorigenesis, but their role in oncogene inactivation-mediated tumor regression is unclear. Here, we show that an intact immune system, specifically CD4+ T cells, is required for the induction of cellular senescence, shutdown of angiogenesis, and chemokine expression resulting in sustained tumor regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T cell acute lymphoblastic lymphoma and pro-B cell leukemia, respectively. Moreover, immune effectors knocked out for thrombospondins failed to induce sustained tumor regression. Hence, CD4+ T cells are required for the remodeling of the tumor microenvironment through the expression of chemokines, such as thrombospondins, in order to elicit oncogene addiction.
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U2 - 10.1016/j.ccr.2010.10.002
DO - 10.1016/j.ccr.2010.10.002
M3 - Article
C2 - 21035406
AN - SCOPUS:78249257291
SN - 1535-6108
VL - 18
SP - 485
EP - 498
JO - Cancer cell
JF - Cancer cell
IS - 5
ER -