Immunologic Research

, Volume 58, Issue 2–3, pp 282–291 | Cite as

An essential role for the immune system in the mechanism of tumor regression following targeted oncogene inactivation

  • Stephanie C. Casey
  • Yulin Li
  • Dean W. FelsherEmail author


Tumors are genetically complex and can have a multitude of mutations. Consequently, it is surprising that the suppression of a single oncogene can result in rapid and sustained tumor regression, illustrating the concept that cancers are often “oncogene addicted.” The mechanism of oncogene addiction has been presumed to be largely cell autonomous as a consequence of the restoration of normal physiological programs that induce proliferative arrest, apoptosis, differentiation, and/or cellular senescence. Interestingly, it has recently become apparent that upon oncogene inactivation, the immune response is critical in mediating the phenotypic consequences of oncogene addiction. In particular, CD4+ T cells have been suggested to be essential to the remodeling of the tumor microenvironment, including the shutdown of host angiogenesis and the induction of cellular senescence in the tumor. However, adaptive and innate immune cells are likely involved. Thus, the effectors of the immune system are involved not only in tumor initiation, tumor progression, and immunosurveillance, but also in the mechanism of tumor regression upon targeted oncogene inactivation. Hence, oncogene inactivation may be an effective therapeutic approach because it both reverses the neoplastic state within a cancer cell and reactivates the host immune response that remodels the tumor microenvironment.


Oncogene addiction MYC Tumor recurrence Tumor microenvironment Tumor immunology 



The authors acknowledge current and former members of the Felsher laboratory. Within the Felsher laboratory, research has been funded by the Burroughs Welcome Fund Career Award, the Damon Runyon Foundation Lilly Clinical Investigator Award, NIH RO1 Grant Number CA 089305, 105102, 170378 PQ22, U54CA149145, U54CA143907, 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, and the Leukemia and Lymphoma Society Translational Research Grant Number R6223-07 (D.W.F.). S.C.C. was previously supported by the Stanford University Cellular and Molecular Immunobiology Training Grant (NIH, 5 T32 AI07290) and is currently supported by an NIH NRSA from the NCI (F32CA177139).

Conflict of interests

The authors declare no competing financial interests.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Stephanie C. Casey
    • 1
  • Yulin Li
    • 1
  • Dean W. Felsher
    • 1
    Email author
  1. 1.Division of Oncology, Departments of Medicine and PathologyStanford University School of MedicineStanfordUSA

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