Immune Checkpoint Blockade in Infectious Diseases

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2017 Oct 10

PMID 28990586

Citations 290

Authors

Michelle N Wykes

Sharon R Lewin

Affiliations

Soon will be listed here.

Abstract

The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus. These pathways are important for preventing immune-driven pathology but can also limit immune-mediated clearance of the infection. The recent success of immune checkpoint blockade in cancer therapy suggests that targeting these pathways would also be effective for preventing and treating a range of infectious diseases. Here, we review our current understanding of immune checkpoint pathways in the pathogenesis of infectious diseases and discuss the potential for therapeutically targeting these pathways in this setting.

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References

Maini M, Boni C, Lee C, Larrubia J, Reignat S, Ogg G . The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med. 2000; 191(8):1269-80. PMC: 2193131. DOI: 10.1084/jem.191.8.1269. View

Akhmetzyanova I, Drabczyk M, Neff C, Gibbert K, Dietze K, Werner T . PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing. PLoS Pathog. 2015; 11(10):e1005224. PMC: 4617866. DOI: 10.1371/journal.ppat.1005224. View

Hisaeda H, Hamano S, Mitoma-Obata C, Tetsutani K, Imai T, Waldmann H . Resistance of regulatory T cells to glucocorticoid-induced [corrected] TNFR family-related protein (GITR) during Plasmodium yoelii infection. Eur J Immunol. 2005; 35(12):3516-24. DOI: 10.1002/eji.200526073. View

Tousif S, Singh Y, Raghava Prasad D, Sharma P, Van Kaer L, Das G . T cells from Programmed Death-1 deficient mice respond poorly to Mycobacterium tuberculosis infection. PLoS One. 2011; 6(5):e19864. PMC: 3093409. DOI: 10.1371/journal.pone.0019864. View

Guidotti L, Isogawa M, Chisari F . Host-virus interactions in hepatitis B virus infection. Curr Opin Immunol. 2015; 36:61-6. PMC: 4593767. DOI: 10.1016/j.coi.2015.06.016. View

Urbani S, Amadei B, Tola D, Pedrazzi G, Sacchelli L, Cavallo M . Restoration of HCV-specific T cell functions by PD-1/PD-L1 blockade in HCV infection: effect of viremia levels and antiviral treatment. J Hepatol. 2008; 48(4):548-58. DOI: 10.1016/j.jhep.2007.12.014. View

Schweitzer A, Horn J, Mikolajczyk R, Krause G, Ott J . Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015; 386(10003):1546-55. DOI: 10.1016/S0140-6736(15)61412-X. View

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

Wherry E . T cell exhaustion. Nat Immunol. 2011; 12(6):492-9. DOI: 10.1038/ni.2035. View

10.

Horne-Debets J, Faleiro R, Karunarathne D, Liu X, Lineburg K, Poh C . PD-1 dependent exhaustion of CD8+ T cells drives chronic malaria. Cell Rep. 2013; 5(5):1204-13. DOI: 10.1016/j.celrep.2013.11.002. View

11.

Tauriainen J, Scharf L, Frederiksen J, Naji A, Ljunggren H, Sonnerborg A . Perturbed CD8 T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals. Sci Rep. 2017; 7:40354. PMC: 5233961. DOI: 10.1038/srep40354. View

12.

Zhou Q, Munger M, Veenstra R, Weigel B, Hirashima M, Munn D . Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood. 2011; 117(17):4501-10. PMC: 3099570. DOI: 10.1182/blood-2010-10-310425. View

13.

Weber J, Postow M, Lao C, Schadendorf D . Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents. Oncologist. 2016; 21(10):1230-1240. PMC: 5061539. DOI: 10.1634/theoncologist.2016-0055. View

14.

Kelesidis T, Jackson N, McComsey G, Wang X, Elashoff D, Dube M . Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection. AIDS. 2016; 30(17):2625-2633. PMC: 5083154. DOI: 10.1097/QAD.0000000000001238. View

15.

Cai G, Freeman G . The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T-cell activation. Immunol Rev. 2009; 229(1):244-58. DOI: 10.1111/j.1600-065X.2009.00783.x. View

16.

Shin T, Kennedy G, Gorski K, Tsuchiya H, Koseki H, Azuma M . Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor. J Exp Med. 2003; 198(1):31-8. PMC: 2196092. DOI: 10.1084/jem.20030242. View

17.

Sharma S, Sundararajan A, Suryawanshi A, Kumar N, Veiga-Parga T, Kuchroo V . T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses. Proc Natl Acad Sci U S A. 2011; 108(47):19001-6. PMC: 3223445. DOI: 10.1073/pnas.1107087108. View

18.

Brahmer J, Tykodi S, Chow L, Hwu W, Topalian S, Hwu P . Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012; 366(26):2455-65. PMC: 3563263. DOI: 10.1056/NEJMoa1200694. View

19.

Zhang Y, Chung Y, Bishop C, Daugherty B, Chute H, Holst P . Regulation of T cell activation and tolerance by PDL2. Proc Natl Acad Sci U S A. 2006; 103(31):11695-700. PMC: 1544232. DOI: 10.1073/pnas.0601347103. View

20.

Brown J, Dorfman D, Ma F, Sullivan E, Munoz O, Wood C . Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol. 2003; 170(3):1257-66. DOI: 10.4049/jimmunol.170.3.1257. View