Reinforcing the Immunocompromised Host Defense Against Fungi: Progress Beyond the Current State of the Art

Overview

Journal J Fungi (Basel)

Date 2021 Jul 2

PMID 34204025

Citations 5

Authors

Georgios Karavalakis

Evangelia Yannaki

Anastasia Papadopoulou

Affiliations

Soon will be listed here.

Abstract

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed.

Citing Articles

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Special Issue: Host Defense against Fungi.

Bliss J J Fungi (Basel). 2021; 7(12).

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References

Barker J, Doubrovina E, Sauter C, Jaroscak J, Perales M, Doubrovin M . Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Blood. 2010; 116(23):5045-9. PMC: 3012598. DOI: 10.1182/blood-2010-04-281873. View

Roemhild A, Reinke P . Virus-specific T-cell therapy in solid organ transplantation. Transpl Int. 2015; 29(5):515-26. DOI: 10.1111/tri.12659. View

Liles W, Huang J, Van Burik J, Bowden R, Dale D . Granulocyte colony-stimulating factor administered in vivo augments neutrophil-mediated activity against opportunistic fungal pathogens. J Infect Dis. 1997; 175(4):1012-5. DOI: 10.1086/513961. View

Hernandez-Chavez M, Perez-Garcia L, Nino-Vega G, Mora-Montes H . Fungal Strategies to Evade the Host Immune Recognition. J Fungi (Basel). 2018; 3(4). PMC: 5753153. DOI: 10.3390/jof3040051. View

Basar R, Daher M, Uprety N, Gokdemir E, Alsuliman A, Ensley E . Large-scale GMP-compliant CRISPR-Cas9-mediated deletion of the glucocorticoid receptor in multivirus-specific T cells. Blood Adv. 2020; 4(14):3357-3367. PMC: 7391161. DOI: 10.1182/bloodadvances.2020001977. View

Uhlin M, Gertow J, Uzunel M, Okas M, Berglund S, Watz E . Rapid salvage treatment with virus-specific T cells for therapy-resistant disease. Clin Infect Dis. 2012; 55(8):1064-73. DOI: 10.1093/cid/cis625. View

Rachini A, Pietrella D, Lupo P, Torosantucci A, Chiani P, Bromuro C . An anti-beta-glucan monoclonal antibody inhibits growth and capsule formation of Cryptococcus neoformans in vitro and exerts therapeutic, anticryptococcal activity in vivo. Infect Immun. 2007; 75(11):5085-94. PMC: 2168274. DOI: 10.1128/IAI.00278-07. View

Conti H, Gaffen S . IL-17-Mediated Immunity to the Opportunistic Fungal Pathogen Candida albicans. J Immunol. 2015; 195(3):780-8. PMC: 4507294. DOI: 10.4049/jimmunol.1500909. View

Leen A, Bollard C, Mendizabal A, Shpall E, Szabolcs P, Antin J . Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013; 121(26):5113-23. PMC: 3695359. DOI: 10.1182/blood-2013-02-486324. View

10.

Peggs K, Verfuerth S, Pizzey A, Khan N, Guiver M, Moss P . Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. Lancet. 2003; 362(9393):1375-7. DOI: 10.1016/S0140-6736(03)14634-X. View

11.

Bollard C, Heslop H . T cells for viral infections after allogeneic hematopoietic stem cell transplant. Blood. 2016; 127(26):3331-40. PMC: 4929925. DOI: 10.1182/blood-2016-01-628982. View

12.

Moosmann A, Bigalke I, Tischer J, Schirrmann L, Kasten J, Tippmer S . Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Blood. 2010; 115(14):2960-70. DOI: 10.1182/blood-2009-08-236356. View

13.

Heslop H, Slobod K, Pule M, Hale G, Rousseau A, Smith C . Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2009; 115(5):925-35. PMC: 2817637. DOI: 10.1182/blood-2009-08-239186. View

14.

Papadopoulou A, Kaloyannidis P, Yannaki E, Cruz C . Adoptive transfer of Aspergillus-specific T cells as a novel anti-fungal therapy for hematopoietic stem cell transplant recipients: Progress and challenges. Crit Rev Oncol Hematol. 2015; 98:62-72. DOI: 10.1016/j.critrevonc.2015.10.005. View

15.

Sun Z, Zhu P, Li L, Wan Z, Zhao Z, Li R . Adoptive immunity mediated by HLA-A*0201 restricted Asp f16 peptides-specific CD8+ T cells against Aspergillus fumigatus infection. Eur J Clin Microbiol Infect Dis. 2012; 31(11):3089-96. DOI: 10.1007/s10096-012-1670-2. View

16.

Koukoulias K, Papayanni P, Georgakopoulou A, Alvanou M, Laidou S, Kouimtzidis A . "Cerberus" T Cells: A Glucocorticoid-Resistant, Multi-Pathogen Specific T Cell Product to Fight Infections in Severely Immunocompromised Patients. Front Immunol. 2021; 11:608701. PMC: 7848034. DOI: 10.3389/fimmu.2020.608701. View

17.

Withers B, Blyth E, Clancy L, Yong A, Fraser C, Burgess J . Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells. Blood Adv. 2018; 1(24):2193-2205. PMC: 5737128. DOI: 10.1182/bloodadvances.2017010223. View

18.

Roilides E, Farmaki E . Granulocyte colony-stimulating factor and other cytokines in antifungal therapy. Clin Microbiol Infect. 2001; 7 Suppl 2:62-7. DOI: 10.1111/j.1469-0691.2001.tb00011.x. View

19.

Stuehler C, Kuenzli E, Jaeger V, Baettig V, Ferracin F, Rajacic Z . Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation and Association With Occurrence and Outcome of Invasive Aspergillosis. J Infect Dis. 2015; 212(6):959-67. DOI: 10.1093/infdis/jiv143. View

20.

Low C, Rotstein C . Emerging fungal infections in immunocompromised patients. F1000 Med Rep. 2011; 3:14. PMC: 3155160. DOI: 10.3410/M3-14. View