Abstract
Background
PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. The PTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models of Pten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy. Recent studies demonstrate that PTEN also regulates immune functionality.
Objective
To understand the multifaceted functions of PTEN as both a tumor suppressor and an immune regulator.
Methods
This review will summarize the emerging knowledge of PTEN function in cancer immunoediting. In addition, the mechanisms underlying functional integration of various PTEN pathways in regulating cancer evolution and tumor immunity will be highlighted.
Results
Recent preclinical and clinical studies revealed the essential role of PTEN in maintaining immune homeostasis, which significantly expands the repertoire of PTEN functions. Mechanistically, aberrant PTEN signaling alters the interplay between the immune system and tumors, leading to immunosuppression and tumor escape.
Conclusion
Rational design of personalized anti-cancer treatment requires mechanistic understanding of diverse PTEN signaling pathways in modulation of the crosstalk between tumor and immune cells.
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References
Anzelon A N, Wu H, Rickert R C (2003). Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function. Nat Immunol, 4(3): 287–294
Bassi C, Ho J, Srikumar T, Dowling R J, Gorrini C, Miller S J, Mak T W, Neel B G, Raught B, Stambolic V (2013). Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science, 341(6144): 395–399
Biggs W H 3rd, Meisenhelder J, Hunter T, Cavenee W K, Arden K C (1999). Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA, 96(13): 7421–7426
Bronisz A, Godlewski J, Wallace J A, Merchant A S, Nowicki M O, Mathsyaraja H, Srinivasan R, Trimboli A J, Martin C K, Li F, Yu L, Fernandez S A, Pécot T, Rosol T J, Cory S, Hallett M, Park M, Piper M G, Marsh C B, Yee L D, Jimenez R E, Nuovo G, Lawler S E, Chiocca E A, Leone G, Ostrowski M C (2012). Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320. Nat Cell Biol, 14(2): 159–167
Brunet A, Bonni A, Zigmond M J, Lin M Z, Juo P, Hu L S, Anderson M J, Arden K C, Blenis J, Greenberg M E (1999). Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 96(6): 857–868
Bucheit A D, Chen G, Siroy A, Tetzlaff M, Broaddus R, Milton D, Fox P, Bassett R, Hwu P, Gershenwald J E, Lazar A J, Davies M A (2014). Complete loss of PTEN protein expression correlates with shorter time to brain metastasis and survival in stage IIIB/C melanoma patients with BRAFV600 mutations. Clin Cancer Res, 20(21): 5527–5536
Buckler J L, Walsh P T, Porrett P M, Choi Y, Turka L A (2006). Cutting edge: T cell requirement for CD28 costimulation is due to negative regulation of TCR signals by PTEN. J Immunol, 177(7): 4262–4266
Chen H H, Handel N, Ngeow J, Muller J, Huhn M, Yang H T, Heindl M, Berbers R M, Hegazy A N, Kionke J, Travis S, Merkenschlager A, Kiess W, Wittekind C, Walker L, Ehl S, Yehia L, Sack U, Blaser R, Rensing-Ehl A, Reifenberger J, Keith J (2016). Immune dysregulation in patients with PTEN hamartoma tumor syndrome: Analysis of FOXP3 regulatory T cells. J Allergy Clin Immunol, 139(2): 607–620
Chen R, Kim O, Yang J, Sato K, Eisenmann K M, McCarthy J, Chen H, Qiu Y (2001). Regulation of Akt/PKB activation by tyrosine phosphorylation. J Biol Chem, 276(34): 31858–31862
Chen Z, Trotman L C, Shaffer D, Lin H K, Dotan Z A, Niki M, Koutcher J A, Scher H I, Ludwig T, Gerald W, Cordon-Cardo C, Paolo Pandolfi P (2005). Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature, 436(7051): 725–730
Chen Z H, Zhu M, Yang J, Liang H, He J, He S, Wang P, Kang X, McNutt M A, Yin Y, Shen W H (2014). PTEN interacts with histone H1 and controls chromatin condensation. Cell Reports, 8(6): 2003–2014
Crellin N K, Garcia R V, Levings M K (2007). Altered activation of AKT is required for the suppressive function of human CD4+CD25+ T regulatory cells. Blood, 109(5): 2014–2022
Dave B, Migliaccio I, Gutierrez MC, Wu MF, Chamness G C, Wong H, Narasanna A, Chakrabarty A, Hilsenbeck S G, Huang J, Rimawi M, Schiff R, Arteaga C, Osborne C K, Chang J C (2011). Loss of phosphatase and tensin homolog or phosphoinositol-3 kinase activation and response to trastuzumab or lapatinib in human epidermal growth factor receptor 2-overexpressing locally advanced breast cancers. J Clin Oncol, 29(2): 166–173
Delgoffe G M, Woo S R, Turnis M E, Gravano D M, Guy C, Overacre A E, Bettini M L, Vogel P, Finkelstein D, Bonnevier J, Workman C J, Vignali D A A (2013). Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature, 501 (7466): 252–256
Di Cristofano A, Kotsi P, Peng Y F, Cordon-Cardo C, Elkon K B, Pandolfi P P (1999). Impaired Fas response and autoimmunity in Pten+/– mice. Science, 285(5436): 2122–2125
Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi P P (1998). Pten is essential for embryonic development and tumour suppression. Nat Genet, 19(4): 348–355
Dunn G P, Bruce A T, Ikeda H, Old L J, Schreiber R D (2002). Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol, 3(11): 991–998
Eppihimer M J, Gunn J, Freeman G J, Greenfield E A, Chernova T, Erickson J, Leonard J P (2002). Expression and regulation of the PDL1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation, 9(2): 133–145
Feng J, Liang J, Li J, Li Y, Liang H, Zhao X, McNuttMA, Yin Y (2015). PTEN Controls the DNA Replication Process through MCM2 in Response to Replicative Stress. Cell Reports, 13(7): 1295–1303
Francisco L M, Salinas V H, Brown K E, Vanguri V K, Freeman G J, Kuchroo V K, Sharpe A H (2009). PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med, 206(13): 3015–3029
Galon J, Angell H K, Bedognetti D, Marincola F M (2013). The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity, 39(1): 11–26
Garcia-Cao I, SongM S, Hobbs R M, Laurent G, Giorgi C, de Boer V C, Anastasiou D, Ito K, Sasaki A T, Rameh L, Carracedo A, Vander HeidenMG, Cantley L C, Pinton P, HaigisMC, Pandolfi P P (2012). Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell, 149(1): 49–62
Gong L, Govan J M, Evans E B, Dai H, Wang E, Lee S W, Lin H K, Lazar A J, Mills G B, Lin S Y (2015). Nuclear PTEN tumorsuppressor functions through maintaining heterochromatin structure. Cell Cycle, 14(14): 2323–2332
Hanahan D, Weinberg R A (2011). Hallmarks of cancer: the next generation. Cell, 144(5): 646–674
He J, Kang X, Yin Y, Chao K S, Shen W H (2015). PTEN regulates DNA replication progression and stalled fork recovery. Nat Commun, 6: 7620
He J, Zhang Z, Ouyang M, Yang F, Hao H, Lamb K L, Yang J, Yin Y, Shen W H (2016). PTEN regulates EG5 to control spindle architecture and chromosome congression during mitosis. Nat Commun, 7: 12355
Hildebrandt MA, Yang H, HungM C, Izzo J G, Huang M, Lin J, Ajani J A, Wu X (2009). Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy. J Clin Oncol, 27(6): 857–871
Hsieh C S, Lee H M, Lio C W (2012). Selection of regulatory T cells in the thymus. Nat Rev Immunol, 12(3): 157–167
Huynh A, Du Page M, Priyadharshini B, Sage P T, Quiros J, Borges C M, Townamchai N, Gerriets V A, Rathmell J C, Sharpe A H, Bluestone J A, Turka L A (2015). Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability. Nat Immunol, 16(2): 188–196
Jiang H, Hegde S, Knolhoff B L, Zhu Y, Herndon J M, Meyer M A, Nywening T M, Hawkins W G, Shapiro I M, Weaver D T, Pachter J A, Wang-Gillam A, De Nardo D G (2016). Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med, 22(8): 851–860
Josefowicz S Z, Lu L F, Rudensky A Y (2012). Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol, 30:531–564
Kane L P, Andres P G, Howland K C, Abbas A K, Weiss A (2001). Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-gamma but not TH2 cytokines. Nat Immunol, 2(1): 37–44
Kang X, Song C, Du X, Zhang C, Liu Y, Liang L, He J, Lamb K, ShenW H, Yin Y (2015). PTEN stabilizes TOP2A and regulates the DNA decatenation. Sci Rep, 5:17873
Komatsu N, Okamoto K, Sawa S, Nakashima T, Oh-hora M, Kodama T, Tanaka S, Bluestone J A, Takayanagi H (2014). Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat Med, 20(1): 62–68
Kral J B, Kuttke M, Schrottmaier W C, Birnecker B, Warszawska J, Wernig C, Paar H, Salzmann M, Sahin E, Brunner J S, Österreicher C, Knapp S, Assinger A, Schabbauer G (2016). Sustained PI3K Activation exacerbates BLM-induced Lung Fibrosis via activation of pro-inflammatory and pro-fibrotic pathways. Sci Rep, 6: 23034
Kritikou E (2007). PTEN- a new guardian of the genome. Nat Rev Mol Cell Biol, 8(3): 179
Lee J J, Kim B C, Park M J, Lee Y S, Kim Y N, Lee B L, Lee J S (2011). PTEN status switches cell fate between premature senescence and apoptosis in glioma exposed to ionizing radiation. Cell Death Differ, 18(4): 666–677
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang S I, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner S H, Giovanella B C, Ittmann M, Tycko B, Hibshoosh H, Wigler M H, Parsons R (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 275(5308): 1943–1947
Li Y, Jia Y, Pichavant M, Loison F, Sarraj B, Kasorn A, You J, Robson B E, Umetsu D T, Mizgerd J P, Ye K, Luo H R (2009). Targeted deletion of tumor suppressor PTEN augments neutrophil function and enhances host defense in neutropenia-associated pneumonia. Blood, 113(20): 4930–4941
Loke P, Allison J P (2003). PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells. Proc Natl Acad Sci USA, 100(9): 5336–5341
Maehama T, Dixon J E (1998). The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem, 273(22): 13375–13378
McEllin B, Camacho C V, Mukherjee B, Hahm B, Tomimatsu N, Bachoo R M, Burma S (2010). PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors. Cancer Res, 70(13): 5457–5464
Mendes-Pereira A M, Martin S A, Brough R, McCarthy A, Taylor J R, Kim J S, Waldman T, Lord C J, Ashworth A (2009). Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med, 1(6–7): 315–322
Michalek R D, Gerriets V A, Jacobs S R, Macintyre A N, Mac Iver N J, Mason E F, Sullivan S A, Nichols A G, Rathmell J C (2011). Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol, 186(6): 3299–3303
Nardella C, Clohessy J G, Alimonti A, Pandolfi P P (2011). Prosenescence therapy for cancer treatment. Nat Rev Cancer, 11(7): 503–511
Newton R, Priyadharshini B, Turka L A (2016). Immunometabolism of regulatory T cells. Nat Immunol, 17(6): 618–625
Ortega-Molina A, Efeyan A, Lopez-Guadamillas E, Munoz-Martin M, Gomez-Lopez G, Canamero M, Mulero F, Pastor J, Martinez S, Romanos E, Mar Gonzalez-Barroso M, Rial E, Valverde A M, Bischoff J R, Serrano M (2012). Pten positively regulates brown adipose function, energy expenditure, and longevity. Cell Metab, 15 (3): 382–394
Ouyang W, Liao W, Luo C T, Yin N, Huse M, Kim M V, Peng M, Chan P, Ma Q, Mo Y, Meijer D, Zhao K, Rudensky A Y, Atwal G, Zhang M Q, Li M O (2012). Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature, 491(7425): 554–559
Pan F, Yu H, Dang E V, Barbi J, Pan X, Grosso J F, Jinasena D, Sharma S M, McCadden E M, Getnet D, Drake C G, Liu J O, Ostrowski MC, Pardoll D M (2009). Eos mediates Foxp3-dependent gene silencing in CD4 + regulatory T cells. Science, 325(5944): 1142–1146
Papa A, Wan L, Bonora M, Salmena L, Song M S, Hobbs R M, Lunardi A, Webster K, Ng C, Newton R H, Knoblauch N, Guarnerio J, Ito K, Turka L A, Beck A H, Pinton P, Bronson R T, Wei W, Pandolfi P P (2014). Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. Cell, 157(3): 595–610
Parsa A T, Waldron J S, Panner A, Crane C A, Parney I F, Barry J J, Cachola K E, Murray J C, Tihan T, Jensen M C, Mischel P S, Stokoe D, Pieper R O (2007). Loss of tumor suppressor PTEN function increases B7–H1 expression and immunoresistance in glioma. Nat Med, 13(1): 84–88
Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell L N, Karoly E D, Freeman G J, Petkova V, Seth P, Li L, Boussiotis V A (2015). PD- 1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun, 6: 6692
Patsoukis N, Li L, Sari D, Petkova V, Boussiotis V A (2013). PD-1 increases PTEN phosphatase activity while decreasing PTEN protein stability by inhibiting casein kinase 2. Mol Cell Biol, 33(16): 3091–3098
Peng W, Chen J Q, Liu C, Malu S, Creasy C, Tetzlaff M T, Xu C, McKenzie J A, Zhang C, Liang X, Williams L J, Deng W, Chen G, Mbofung R, Lazar A J, Torres-Cabala C A, Cooper Z A, Chen P L, Tieu T N, Spranger S, Yu X, Bernatchez C, ForgetMA, Haymaker C, Amaria R, McQuade J L, Glitza I C, Cascone T, Li H S, Kwong L N, Heffernan T P, Hu J, Bassett R L, Bosenberg M W, Woodman S E, Overwijk W W, Lizee G, Roszik J, Gajewski T F, Wargo J A, Gershenwald J E, Radvanyi L, Davies M A, Hwu P (2016). Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy. Cancer Discov, 6(2): 202–216
Podsypanina K, Ellenson L H, Nemes A, Gu J, Tamura M, Yamada K M, Cordon-Cardo C, Catoretti G, Fisher P E, Parsons R (1999). Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc Natl Acad Sci USA, 96(4): 1563–1568
Riou C, Yassine-Diab B, Van grevenynghe J, Somogyi R, Greller L D, Gagnon D, Gimmig S, Wilkinson P, Shi Y, Cameron M J, Campos- Gonzalez R, Balderas R S, Kelvin D, Sekaly R P, Haddad E K (2007). Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells. J Exp Med, 204(1): 79–91
Schreiber R D, Old L J, Smyth M J (2011). Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science, 331(6024): 1565–1570
Sharma M D, Huang L, Choi J H, Lee E J, Wilson J M, Lemos H, Pan F, Blazar B R, Pardoll D M, Mellor A L, Shi H, Munn D H (2013). An inherently bifunctional subset of Foxp3+ T helper cells is controlled by the transcription factor eos. Immunity, 38(5): 998–1012
Sharma M D, Shinde R, McGaha T L, Huang L, Holmgaard R B, Wolchok J D, Mautino M R, Celis E, Sharpe A H, Francisco L M, Powell J D, Yagita H, Mellor A L, Blazar B R, Munn D H (2015). The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment. Sci Adv, 1(10): e1500845
Sharma P, Allison J P (2015). The future of immune checkpoint therapy. Science, 348(6230): 56–61
Shen W H, Balajee A S, Wang J, Wu H, Eng C, Pandolfi P P, Yin Y (2007). Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell, 128(1): 157–170
Shi L Z, Wang R, Huang G, Vogel P, Neale G, Green D R, Chi H (2011). HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med, 208(7): 1367–1376
Shrestha S, Yang K, Guy C, Vogel P, Neale G, Chi H (2015). Treg cells require the phosphatase PTEN to restrain TH1 and TFH cell responses. Nat Immunol, 16(2): 178–187
Song M S, Carracedo A, Salmena L, Song S J, Egia A, Malumbres M, Pandolfi P P (2011). Nuclear PTEN regulates the APC-CDH1 tumorsuppressive complex in a phosphatase-independent manner. Cell, 144 (2): 187–199
Soond D R, Garcon F, Patton D T, Rolf J, Turner M, Scudamore C, Garden O A, Okkenhaug K (2012). Pten loss in CD4 T cells enhances their helper function but does not lead to autoimmunity or lymphoma. J Immunol, 188(12): 5935–5943
Stambolic V, Tsao M S, Macpherson D, Suzuki A, Chapman W B, Mak T W (2000). High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/– mice. Cancer Res, 60(13): 3605–3611
Steck P A, Pershouse M A, Jasser S A, Yung W K, Lin H, Ligon A H, Langford L A, Baumgard M L, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng D H R, Tavtigian S V (1997). Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet, 15(4): 356–362
Subramanian K K, Jia Y, Zhu D, Simms B T, Jo H, Hattori H, You J, Mizgerd J P, Luo H R (2007). Tumor suppressor PTEN is a physiologic suppressor of chemoattractant-mediated neutrophil functions. Blood, 109(9): 4028–4037
Sun Z, Huang C, He J, Lamb K L, Kang X, Gu T, Shen W H, Yin Y (2014). PTEN C-terminal deletion causes genomic instability and tumor development. Cell Reports, 6(5): 844–854
Suzuki A, Yamaguchi M T, Ohteki T, Sasaki T, Kaisho T, Kimura Y, Yoshida R, Wakeham A, Higuchi T, Fukumoto M, Tsubata T, Ohashi P S, Koyasu S, Penninger J M, Nakano T, Mak T W (2001). T cellspecific loss of Pten leads to defects in central and peripheral tolerance. Immunity, 14(5): 523–534
Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, Yamada KM (1998). Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science, 280(5369): 1614–1617
Teng M W, Galon J, Fridman W H, Smyth M J (2015). From mice to humans: developments in cancer immunoediting. J Clin Invest, 125 (9): 3338–3346
Terawaki S, Chikuma S, Shibayama S, Hayashi T, Yoshida T, Okazaki T, Honjo T (2011). IFN-alpha directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J Immunol, 186(5): 2772–2779
Torres J, Pulido R (2001). The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J Biol Chem, 276(2): 993–998
Toso A, Revandkar A, Di Mitri D, Guccini I, Proietti M, Sarti M, Pinton S, Zhang J, Kalathur M, Civenni G, Jarrossay D, Montani E, Marini C, Garcia-Escudero R, Scanziani E, Grassi F, Pandolfi P P, Catapano C V, Alimonti A (2014). Enhancing chemotherapy efficacy in Ptendeficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Reports, 9(1): 75–89
Trimboli A J, Cantemir-Stone C Z, Li F, Wallace J A, Merchant A, Creasap N, Thompson J C, Caserta E, Wang H, Chong J L, Naidu S, Wei G, Sharma S M, Stephens J A, Fernandez S A, Gurcan M N, Weinstein M B, Barsky S H, Yee L, Rosol T J, Stromberg P C, Robinson ML, Pepin F, Hallett M, Park M, Ostrowski MC, Leone G (2009). Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature, 461(7267): 1084–1091
van Ree J H, Nam H J, Jeganathan K B, Kanakkanthara A, van Deursen J M (2016). Pten regulates spindle pole movement through Dlg1- mediated recruitment of Eg5 to centrosomes. Nat Cell Biol, 18(7): 814–821
Vazquez F, Ramaswamy S, Nakamura N, Sellers W R (2000). Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol, 20(14): 5010–5018
Vesely M D, KershawM H, Schreiber R D, Smyth M J (2011). Natural innate and adaptive immunity to cancer. Annu Rev Immunol, 29: 235–271
Wang G, Li Y, Wang P, Liang H, Cui M, Zhu M, Guo L, Su Q, Sun Y, McNutt M A, Yin Y (2015). PTEN regulates RPA1 and protects DNA replication forks. Cell Res, 25(11): 1189–1204
Yadav M, Louvet C, Davini D, Gardner JM, Martinez M- Llordella S, Bailey-Bucktrout B A, Anthony F M, Sverdrup R, Head D J, Kuster P, Ruminski D, Weiss D, V J Aon Schack, Bluestone (2012). Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med, 209(10): 1713–1722, S1711–1719
Yin Y, Shen W H (2008). PTEN: a new guardian of the genome. Oncogene, 27(41): 5443–5453
Zhang Z, Hou S Q, He J, Gu T, Yin Y, Shen W H (2016). PTEN regulates PLK1 and controls chromosomal stability during cell division. Cell Cycle, 15(18): 2476–2485
Acknowledgements
Work in the authors’ laboratory is supported by NIH grant R01GM100478 and the Irma T. Hirschl/Monique Weill-Caulier Trust.
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Brandmaier, A., Hou, SQ., Demaria, S. et al. PTEN at the interface of immune tolerance and tumor suppression. Front. Biol. 12, 163–174 (2017). https://doi.org/10.1007/s11515-017-1443-5
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DOI: https://doi.org/10.1007/s11515-017-1443-5