Activation of Akt as a mechanism for tumor immune evasion

Kyung Hee Noh, Tae Heung Kang, Jin Hee Kim, Sara I. Pai, Ken Y. Lin, Chien Fu Hung, T. C. Wu, Tae Woo Kim

Research output: Contribution to journalArticle

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Abstract

Immune evasion is an important reason why the immune system cannot control tumor growth. To elucidate the mechanism for tumor immune evasion, we generated an immune-resistant human papillomavirus type 16 (HPV-16) E7-expressing tumor cell line by subjecting a susceptible tumor cell line to multiple rounds of in vivo immune selection with an E7-specific vaccine. Comparison of parental and immune-resistant tumors revealed that Akt is highly activated in the immune-resistant tumors. Retroviral transfer of a constitutively active form of Akt into the parental tumor significantly increased its resistance against E7-specific CD8+ T-cell mediated apoptosis. The observed resistance against apoptosis was found to be associated with the upregulation of antiapoptotic molecules. We also observed that intratumoral injection of an Akt inhibitor enhanced the therapeutic efficacy of E7-specific vaccine or E7-specific CD8+ T-cell adoptive transfer against the immune-resistant tumors. Thus, our data indicate that the activation of PI3K/Akt pathway represents a new mechanism of immune escape and has important implications for the development of a novel strategy in cancer immunotherapy against immune-resistant tumor cells.

Original languageEnglish
Pages (from-to)439-447
Number of pages9
JournalMolecular Therapy
Volume17
Issue number3
DOIs
Publication statusPublished - 2009 Jan 1

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Tumor Escape
Neoplasms
Tumor Cell Line
Vaccines
Apoptosis
T-Lymphocytes
Immune Evasion
Human papillomavirus 16
Adoptive Transfer
Phosphatidylinositol 3-Kinases
Immunotherapy
Immune System
Up-Regulation
Injections
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Noh, K. H., Kang, T. H., Kim, J. H., Pai, S. I., Lin, K. Y., Hung, C. F., ... Kim, T. W. (2009). Activation of Akt as a mechanism for tumor immune evasion. Molecular Therapy, 17(3), 439-447. https://doi.org/10.1038/mt.2008.255

Activation of Akt as a mechanism for tumor immune evasion. / Noh, Kyung Hee; Kang, Tae Heung; Kim, Jin Hee; Pai, Sara I.; Lin, Ken Y.; Hung, Chien Fu; Wu, T. C.; Kim, Tae Woo.

In: Molecular Therapy, Vol. 17, No. 3, 01.01.2009, p. 439-447.

Research output: Contribution to journalArticle

Noh, KH, Kang, TH, Kim, JH, Pai, SI, Lin, KY, Hung, CF, Wu, TC & Kim, TW 2009, 'Activation of Akt as a mechanism for tumor immune evasion', Molecular Therapy, vol. 17, no. 3, pp. 439-447. https://doi.org/10.1038/mt.2008.255
Noh KH, Kang TH, Kim JH, Pai SI, Lin KY, Hung CF et al. Activation of Akt as a mechanism for tumor immune evasion. Molecular Therapy. 2009 Jan 1;17(3):439-447. https://doi.org/10.1038/mt.2008.255
Noh, Kyung Hee ; Kang, Tae Heung ; Kim, Jin Hee ; Pai, Sara I. ; Lin, Ken Y. ; Hung, Chien Fu ; Wu, T. C. ; Kim, Tae Woo. / Activation of Akt as a mechanism for tumor immune evasion. In: Molecular Therapy. 2009 ; Vol. 17, No. 3. pp. 439-447.
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