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Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity.

Publication ,  Journal Article
Wu, J; Shin, J; Xie, D; Wang, H; Gao, J; Zhong, X-P
Published in: J Immunol
March 15, 2014

Development of effective immune therapies for cancer patients requires better understanding of hurdles that prevent the generation of effective antitumor immune responses. Administration of α-galactosylceramide (α-GalCer) in animals enhances antitumor immunity via activation of the invariant NKT (iNKT) cells. However, repeated injections of α-GalCer result in long-term unresponsiveness or anergy of iNKT cells, severely limiting its efficacy in tumor eradication. The mechanisms leading to iNKT cell anergy remain poorly understood. We report in this study that the tuberous sclerosis 1 (TSC1), a negative regulator of mTOR signaling, plays a crucial role in iNKT cell anergy. Deficiency of TSC1 in iNKT cells results in resistance to α-GalCer-induced anergy, manifested by increased expansion of and cytokine production by iNKT cells in response to secondary Ag stimulation. It is correlated with impaired upregulation of programmed death-1, Egr2, and Grail. Moreover, TSC1-deficient iNKT cells display enhanced antitumor immunity in a melanoma lung metastasis model. Our data suggest targeting TSC1/2 as a strategy for boosting antitumor immune therapy.

Duke Scholars

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2014

Volume

192

Issue

6

Start / End Page

2643 / 2650

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tumor Suppressor Proteins
  • Tuberous Sclerosis Complex 2 Protein
  • Tuberous Sclerosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Programmed Cell Death 1 Receptor
  • Natural Killer T-Cells
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

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Wu, J., Shin, J., Xie, D., Wang, H., Gao, J., & Zhong, X.-P. (2014). Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity. J Immunol, 192(6), 2643–2650. https://doi.org/10.4049/jimmunol.1302076
Wu, Jinhong, Jinwook Shin, Danli Xie, Hongxia Wang, Jimin Gao, and Xiao-Ping Zhong. “Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity.J Immunol 192, no. 6 (March 15, 2014): 2643–50. https://doi.org/10.4049/jimmunol.1302076.
Wu J, Shin J, Xie D, Wang H, Gao J, Zhong X-P. Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity. J Immunol. 2014 Mar 15;192(6):2643–50.
Wu, Jinhong, et al. “Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity.J Immunol, vol. 192, no. 6, Mar. 2014, pp. 2643–50. Pubmed, doi:10.4049/jimmunol.1302076.
Wu J, Shin J, Xie D, Wang H, Gao J, Zhong X-P. Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity. J Immunol. 2014 Mar 15;192(6):2643–2650.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2014

Volume

192

Issue

6

Start / End Page

2643 / 2650

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tumor Suppressor Proteins
  • Tuberous Sclerosis Complex 2 Protein
  • Tuberous Sclerosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Programmed Cell Death 1 Receptor
  • Natural Killer T-Cells
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice