Akt1 and -2 inhibition diminishes terminal differentiation and enhances central memory CD8⁺ T-cell proliferation and survival

References

• Kim EH, Suresh M. Role of PI3K/Akt signaling in memory CD8 T cell differentiation. Front Immunol 2013; 4:20; PMID:23378844
   PubMed Web of Science ®Google Scholar
• Klebanoff CA, Gattinoni L, Restifo NP. CD8+ T-cell memory in tumor immunology and immunotherapy. Immunol Rev 2006; 211:214–24; PMID:16824130; http://dx.doi.org/10.1111/j.0105-2896.2006.00391.x
   PubMed Web of Science ®Google Scholar
• Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401:708–12; PMID:10537110; http://dx.doi.org/10.1038/44385
   PubMed Web of Science ®Google Scholar
• Klebanoff CA, Gattinoni L, Torabi-Parizi P, Kerstann K, Cardones AR, Finkelstein SE, Palmer DC, Antony PA, Hwang ST, Rosenberg SA, et al. Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci U S A 2005; 102:9571–6; PMID:15980149; http://dx.doi.org/10.1073/pnas.0503726102
   PubMed Web of Science ®Google Scholar
• Wherry EJ, Teichgraber V, Becker TC, Masopust D, Kaech SM, Antia R, , von Andrian UH, Ahmed R. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 2003; 4:225–34; PMID:12563257; http://dx.doi.org/10.1038/ni889
   PubMed Web of Science ®Google Scholar
• Rosenberg SA, Sherry RM, Morton KE, Scharfman WJ, Yang JC, Topalian SL, Royal RE, Kammula U, Restifo NP, Hughes MS, et al. Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma. J Immunol 2005; 175:6169–76; PMID:16237114; http://dx.doi.org/10.4049/jimmunol.175.9.6169
   PubMed Web of Science ®Google Scholar
• Roberts AD, Ely KH, Woodland DL. Differential contributions of central and effector memory T cells to recall responses. J Exp Med 2005; 202:123–33; PMID:15983064; http://dx.doi.org/10.1084/jem.20050137
   PubMed Web of Science ®Google Scholar
• Wu F, Zhang W, Shao H, Bo H, Shen H, Li J, et al. Human effector T cells derived from central memory cells rather than CD8T cells modified by tumor-specific TCR gene transfer possess superior traits for adoptive immunotherapy. Cancer Lett 2013; 339(2):195–207.
   Web of Science ®Google Scholar
• Kim EH, Sullivan JA, Plisch EH, Tejera MM, Jatzek A, Choi KY, Suresh M. Signal integration by Akt regulates CD8 T cell effector and memory differentiation. J Immunol 2012; 188:4305–14; PMID:22467649; http://dx.doi.org/10.4049/jimmunol.1103568
   PubMed Web of Science ®Google Scholar
• Finlay D, Cantrell D. Phosphoinositide 3-kinase and the mammalian target of rapamycin pathways control T cell migration. Ann N Y Acad Sci 2010; 1183:149–57; PMID:20146713; http://dx.doi.org/10.1111/j.1749-6632.2009.05134.x
   PubMedGoogle Scholar
• Kane LP, Weiss A. The PI-3 kinase/Akt pathway and T cell activation: pleiotropic pathways downstream of PtdIns(3,4,5)P3. Immunol Rev 2003; 192:7–20; PMID:12670391; http://dx.doi.org/10.1034/j.1600-065X.2003.00008.x
   PubMedGoogle Scholar
• Mao C, Tili EG, Dose M, Haks MC, Bear SE, Maroulakou I, Horie K, Gaitanaris GA, Fidanza V, Ludwig T, et al. Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. J Immunol 2007; 178:5443–53; PMID:17442925; http://dx.doi.org/10.4049/jimmunol.178.9.5443
   PubMedGoogle Scholar
• Juntilla MM, Wofford JA, Birnbaum MJ, Rathmell JC, Koretzky GA. Akt1 and Akt2 are required for alphabeta thymocyte survival and differentiation. Proc Natl Acad Sci U S A 2007; 104:12105–10; PMID:17609365; http://dx.doi.org/10.1073/pnas.0705285104
   PubMed Web of Science ®Google Scholar
• Li Q, Rao R, Vazzana J, Goedegebuure P, Odunsi K, Gillanders W, Shrikant PA. Regulating mammalian target of rapamycin to tune vaccination-induced CD8(+) T cell responses for tumor immunity. J Immunol 2012; 188:3080–7; PMID:22379028; http://dx.doi.org/10.4049/jimmunol.1103365
   PubMed Web of Science ®Google Scholar
• Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, Larsen CP, Ahmed R. mTOR regulates memory CD8 T-cell differentiation. Nature 2009; 460:108–12; PMID:19543266; http://dx.doi.org/10.1038/nature08155
   PubMed Web of Science ®Google Scholar
• Mineharu Y, Kamran N, Lowenstein PR, Castro MG. Blockade of mTOR signaling via rapamycin combined with immunotherapy augments anti-glioma cytotoxic and memory t cells' functions. Mol Cancer Ther 2014; 13(12):3024–36; PMID:25256739
   PubMed Web of Science ®Google Scholar
• Kim HL. Antibody-based depletion of Foxp3+ T cells potentiates antitumor immune memory stimulated by mTOR inhibition. Oncoimmunology 2014; 3:e29081; PMID:25083329; http://dx.doi.org/10.4161/onci.29081
   PubMedGoogle Scholar
• Long SA, Buckner JH. Combination of rapamycin and IL-2 increases de novo induction of human CD4(+)CD25(+)FOXP3(+) T cells. J Autoimmun 2008; 30:293–302; PMID:18313267; http://dx.doi.org/10.1016/j.jaut.2007.12.012
   PubMedGoogle Scholar
• Strauss L, Whiteside TL, Knights A, Bergmann C, Knuth A, Zippelius A. Selective survival of naturally occurring human CD4+CD25+Foxp3+ regulatory T cells cultured with rapamycin. J Immunol 2007; 178:320–9; PMID:17182569; http://dx.doi.org/10.4049/jimmunol.178.1.320
   PubMed Web of Science ®Google Scholar
• Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 2005; 105:4743–8; PMID:15746082; http://dx.doi.org/10.1182/blood-2004-10-3932
   PubMed Web of Science ®Google Scholar
• Basu S, Golovina T, Mikheeva T, June CH, Riley JL. Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin. J Immunol 2008; 180:5794–8; PMID:18424697; http://dx.doi.org/10.4049/jimmunol.180.9.5794
   PubMedGoogle Scholar
• Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, Khuri FR. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 2005; 65:7052–8; PMID:16103051; http://dx.doi.org/10.1158/0008-5472.CAN-05-0917
   PubMed Web of Science ®Google Scholar
• Abu-Eid R, Samara RN, Ozbun L, Abdalla MY, Berzofsky JA, Friedman KM, Mkrtichyan M, Khleif SN. Selective inhibition of regulatory T cells by targeting the PI3K-Akt pathway. Cancer Immunol Res 2014; 2:1080–9; PMID:25080445; http://dx.doi.org/10.1158/2326-6066.CIR-14-0095
   PubMed Web of Science ®Google Scholar
• Wen M, Xu W, Ren L, Gao F, Cui N, Wen J, Li X, Lin L, Ma Z, Chen B, et al. Effector cells derived from naive T cells used in tumor immunotherapy of mice bearing B16 melanoma. Chin Med J (Engl) 2014; 127:1328–33; PMID:24709189
   PubMedGoogle Scholar
• Hinrichs CS, Borman ZA, Gattinoni L, Yu Z, Burns WR, Huang J, Klebanoff CA, Johnson LA, Kerkar SP, Yang S, et al. Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood 2011; 117:808–14; PMID:20971955; http://dx.doi.org/10.1182/blood-2010-05-286286
   PubMed Web of Science ®Google Scholar
• B6.Cg-Thy1a/Cy Tg(TcraTcrb)8Rest/J. The Jackson Laboratory; 2004. Available at: http://jaxmice.jax.org/strain/005023.html
   Google Scholar