Programmed Death-1 Upregulation is Correlated with Dysfunction of Tumor-infiltrating CD8+ T Lymphocytes in Human Non-small Cell Lung Cancer

Overview

Journal Cell Mol Immunol

Date 2010 Jun 2

PMID 20514052

Citations 140

Authors

Yan Zhang

Shengdong Huang

Dejun Gong

Yanghua Qin

Qian Shen

Affiliations

Soon will be listed here.

Abstract

T-cell tolerance is an important mechanism for tumor escape, but the molecular pathways involved in T-cell tolerance remain poorly understood. It remains unknown whether the inhibitory immunoreceptor programmed death-1 (PD-1) plays a role in conditions of human non-small cell lung cancer (NSCLC). In this study, we detected PD-1 expression on CD8+ T cells from healthy control peripheral blood mononuclear cells (PBMCs) and the PBMCs of NSCLC patients as well as NSCLC tissues. Results showed that tumor-infiltrating CD8+ T cells had increased PD-1 expression and impaired immune function, including reducing cytokine production capability and impairing capacity to proliferate. Blockade of the PD-1/PD-L1 pathway by the PD-L1-specific antibody partially restored cytokine production and cell proliferation. These data provide direct evidence that the PD-1/PD-L1 pathway is involved in CD8+ T-cell dysfunction in NSCLC patients. Moreover, blocking this pathway provides a potential therapy target in lung cancer.

Citing Articles

Impact of T Cell Exhaustion and Stroma Senescence on Tumor Cell Biology and Clinical Outcome of Head and Neck Squamous Cell Carcinomas.

Brust L, Vorschel M, Korner S, Knebel M, Kuhn J, Wemmert S Int J Mol Sci. 2025; 25(24.

PMID: 39769271 PMC: 11728369. DOI: 10.3390/ijms252413490.

A novel hydrophobic tag leads to the efficient degradation of programmed death-ligand 1.

Gao J, Xie Y, Zhang J, Chen H, Zou Y, Cen S RSC Med Chem. 2024; 15(9):3038-3047.

PMID: 39309365 PMC: 11411611. DOI: 10.1039/d4md00320a.

Rewiring the T cell-suppressive cytokine landscape of the tumor microenvironment: a new frontier for precision anti-cancer therapy.

Lopresti L, Tatangelo V, Baldari C, Patrussi L Front Immunol. 2024; 15:1418527.

PMID: 39281678 PMC: 11392891. DOI: 10.3389/fimmu.2024.1418527.

Posttranscriptional Events Orchestrate Immune Homeostasis of CD8 T Cells.

Freen-van Heeren J Methods Mol Biol. 2024; 2782:65-80.

PMID: 38622392 DOI: 10.1007/978-1-0716-3754-8_4.

Immune modulation in malignant pleural effusion: from microenvironment to therapeutic implications.

Ge S, Zhao Y, Liang J, He Z, Li K, Zhang G Cancer Cell Int. 2024; 24(1):105.

PMID: 38475858 PMC: 10936107. DOI: 10.1186/s12935-024-03211-w.

References

Barber D, Wherry E, Masopust D, Zhu B, Allison J, Sharpe A . Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2005; 439(7077):682-7. DOI: 10.1038/nature04444. View

Keir M, Butte M, Freeman G, Sharpe A . PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008; 26:677-704. PMC: 10637733. DOI: 10.1146/annurev.immunol.26.021607.090331. View

Brooks D, Lee A, Elsaesser H, McGavern D, Oldstone M . IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection. J Exp Med. 2008; 205(3):533-41. PMC: 2275377. DOI: 10.1084/jem.20071948. View

Petrovas C, Casazza J, Brenchley J, Price D, Gostick E, Adams W . PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med. 2006; 203(10):2281-92. PMC: 2118095. DOI: 10.1084/jem.20061496. View

Zhang M, Tang H, Guo Z, An H, Zhu X, Song W . Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol. 2004; 5(11):1124-33. DOI: 10.1038/ni1130. View

Zhang P, Su D, Liang M, Fu J . Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis. Mol Immunol. 2007; 45(5):1470-6. DOI: 10.1016/j.molimm.2007.08.013. View

Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T . Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol. 2007; 81(8):4215-25. PMC: 1866111. DOI: 10.1128/JVI.02844-06. View

Day C, Kaufmann D, Kiepiela P, Brown J, Moodley E, Reddy S . PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006; 443(7109):350-4. DOI: 10.1038/nature05115. View

Trautmann L, Janbazian L, Chomont N, Said E, Gimmig S, Bessette B . Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med. 2006; 12(10):1198-202. DOI: 10.1038/nm1482. View

10.

Wherry E, Blattman J, Murali-Krishna K, van der Most R, Ahmed R . Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. 2003; 77(8):4911-27. PMC: 152117. DOI: 10.1128/jvi.77.8.4911-4927.2003. View

11.

Zhang J, Zhang Z, Wang X, Fu J, Yao J, Jiao Y . PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors. Blood. 2007; 109(11):4671-8. DOI: 10.1182/blood-2006-09-044826. View

12.

Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C . Cancer statistics, 2006. CA Cancer J Clin. 2006; 56(2):106-30. DOI: 10.3322/canjclin.56.2.106. View

13.

Swann J, Smyth M . Immune surveillance of tumors. J Clin Invest. 2007; 117(5):1137-46. PMC: 1857231. DOI: 10.1172/JCI31405. View

14.

Sharpe A, Wherry E, Ahmed R, Freeman G . The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007; 8(3):239-45. DOI: 10.1038/ni1443. View

15.

Inman B, Sebo T, Frigola X, Dong H, Bergstralh E, Frank I . PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer. 2007; 109(8):1499-505. DOI: 10.1002/cncr.22588. View

16.

Radziewicz H, Ibegbu C, Fernandez M, Workowski K, Obideen K, Wehbi M . Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression. J Virol. 2006; 81(6):2545-53. PMC: 1865979. DOI: 10.1128/JVI.02021-06. View

17.

Blackburn S, Shin H, Nicholas Haining W, Zou T, Workman C, Polley A . Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2008; 10(1):29-37. PMC: 2605166. DOI: 10.1038/ni.1679. View

18.

Carter L, Fouser L, Jussif J, Fitz L, Deng B, Wood C . PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol. 2002; 32(3):634-43. DOI: 10.1002/1521-4141(200203)32:3<634::AID-IMMU634>3.0.CO;2-9. View

19.

Lafferty K, Cunningham A . A new analysis of allogeneic interactions. Aust J Exp Biol Med Sci. 1975; 53(1):27-42. DOI: 10.1038/icb.1975.3. View

20.

Boettler T, Panther E, Bengsch B, Nazarova N, Spangenberg H, Blum H . Expression of the interleukin-7 receptor alpha chain (CD127) on virus-specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J Virol. 2006; 80(7):3532-40. PMC: 1440406. DOI: 10.1128/JVI.80.7.3532-3540.2006. View