CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Rakhra, K; Bachireddy, P; Zabuawala, T; Zeiser, R; Xu, L; Kopelman, A; Fan, AC; Yang, Q; Braunstein, L; Crosby, E; Ryeom, S; Felsher, DW

Published Date

  • November 16, 2010

Published In

Volume / Issue

  • 18 / 5

Start / End Page

  • 485 - 498

PubMed ID

  • 21035406

Pubmed Central ID

  • PMC2991103

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2010.10.002


  • eng

Conference Location

  • United States