Case Report: Immune Checkpoint Blockade Plus Interferon-Γ Add-On Antifungal Therapy in the Treatment of Refractory Covid-Associated Pulmonary Aspergillosis and Cerebral Mucormycosis

Serris, Alexandra; Ouedrani, Amani; Uhel, Fabrice; Gazzano, Marianne; Bedarida, Vincent; Rouzaud, Claire; Bougnoux, Marie‐Elisabeth; Raphalen, Jean-Herlé; Poirée, S.; Lambotte, Olivier; Martin‐Blondel, Guillaume

doi:10.3389/fimmu.2022.900522

Cited by 15 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, combinatorial immunotherapy with nivolumab and IFN-γ was reported in a 56-year-old diabetic patient with COVID-19 who had received dexamethasone and tocilizumab (anti-IL-6) and developed invasive pulmonary aspergillosis one week after intensive-care unit (ICU) admission, later complicated by two Mucoralean brain abscesses and ethmoidal sinusitis ( 55 ). The brain lesions were insufficiently responsive to combined antifungal therapy with liposomal amphotericin B and triazoles, and only partially accessible for surgical debridement.…”

Section: The Growing Promise Of Icis In Medical Mycologymentioning

confidence: 79%

“…Under isavuconazole only, cerebral mucormycosis progressed and the patient deteriorated. The authors discussed that earlier salvage immunotherapy might have had a stronger immunological and clinical impact and underscored the need to study optimal timing of antifungal ICI therapy in the setting of underlying antifungal therapy ( 55 ).…”

Section: The Growing Promise Of Icis In Medical Mycologymentioning

confidence: 99%

“…Additionally, early ICI therapy in a background of high fungal burden and inflammation likely contributed to the reports of considerable toxicities, especially at full oncological dosing of ICIs ( 45 , 47 ). In contrast, all clinical case reports described late-stage application of ICIs in patients with IMIs, a strategy that might have suboptimal efficacy in a setting of severely exhausted and terminally differentiated effector cells ( 55 ). Therefore, the optimal timing of ICI therapy needs to be thoroughly studied in preclinical models.…”

Section: Research Gaps and Future Directionsmentioning

confidence: 99%

See 2 more Smart Citations

Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

2022

View full text Add to dashboard Cite

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic mold infections, and dimorphic fungal infections. We then review the potential merits of immune checkpoint inhibitors (ICIs) as an antifungal immunotherapy, including the incomplete knowledge of the mechanisms involved in both immuno-protective effects and toxicities. In the second part of this review, we discuss the limitations of the current evidence and the many unknowns about ICIs as an antifungal immune enhancement strategy. Based on these gaps of knowledge and lessons learned from cancer immunology studies, we outline a research agenda to determine a “sweet spot” for ICIs in medical mycology. We specifically discuss the importance of more nuanced animal models, the need to study ICI-based combination therapy, potential ICI resistance, the role of the immune microenvironment, and the impact of ICIs given as part of oncological therapies on the natural immunity to various pathogenic fungi.

show abstract

Section: The Growing Promise Of Icis In Medical Mycologymentioning

confidence: 79%

Section: The Growing Promise Of Icis In Medical Mycologymentioning

confidence: 99%

Section: Research Gaps and Future Directionsmentioning

confidence: 99%

See 1 more Smart Citation

Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

2022

View full text Add to dashboard Cite

show abstract

“…Antibody and Tcell responses after COVID-19 vaccinations in a majority of solid tumor patients were equivalent to those of healthy donors [15]. A case report of a diabetic patient with refractory invasive fungal diseases after SARS-CoV-2 infection demonstrated that treatment with ICI and interferon greversed T cell exhaustion and enhance leukocytes activation, whereas careful consideration in immune-mediated adverse events is needed [16]. A cohort study in cancer patients demonstrated that the immune response to COVID vaccination is independent of the anti-cancer immune response in ICI treatment [17].…”

Section: Icis and Covid-19mentioning

confidence: 93%

“…Several recent studies have suggested the relationship between ICIs and COVID-19 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18).A melanoma patient treated with nivolumab, an ICI, and bempegaldesleukin, PEGylated interleukin-2 (IL-2), developed COVID-19 pneumonia with no serious adverse outcome [9], however, modification of the immune response to COVID-19 by treatment with ICIs and bempegaldesleukin has been suggested [9]. Treatment with ICIs, tocilizumab plus pembrolizumab showed decreased time to clinical improvement in COVID-19 patients [10,11].Patients with lung cancer treated with ICIs demonstrated no increased incidence of immune-related adverse events associated with mRNA vaccines, while the vaccine immunogenicity was lower [12].…”

Section: Icis and Covid-19mentioning

confidence: 99%

Relationship Between Corona Virus Infection And Immune Checkpoint Inhibitors

Tanabe¹

2022

Genesis

View full text Add to dashboard Cite

The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) causes infectious disease, COVID-19, and the relationship between COVID-19 and cancer immunotherapy such as immune checkpoint inhibitors (ICIs) is not fully understood. Recent rapid progress in ICI therapy has reported their immune response-related reaction, which demonstrates the importance of studies on the relationship between ICIs and COVID-19. In this Editorial, the application of ICIs in COVID-19 is focused on.

show abstract

Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading

et al. 2023

View full text Add to dashboard Cite

Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients and hence vulnerable hosts increases, which is paralleled by the emergence of a rise in IA cases. Increased frequencies of azole-resistant strains are reported from six continents, presenting a new challenge for the therapeutic management. Treatment options for IA currently consist of three classes of antifungals (azoles, polyenes, echinocandins) with distinctive advantages and shortcomings. Especially in settings of difficult to treat IA, comprising drug tolerance/resistance, limiting drug–drug interactions, and/or severe underlying organ dysfunction, novel approaches are urgently needed. Promising new drugs for the treatment of IA are in late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix (a Gwt1 enzyme inhibitor), ibrexafungerp (a triterpenoid), opelconazole (an azole optimized for inhalation) and rezafungin (an echinocandin with long half-life time). Further, new insights in the pathophysiology of IA yielding immunotherapy as a potential add-on therapy. Current investigations show encouraging results, so far mostly in preclinical settings. In this review we discuss current treatment strategies, give an outlook on possible new pharmaceutical therapeutic options, and, lastly, provide an overview of the ongoing research in immunotherapy for IA.

show abstract

Case Report: Immune Checkpoint Blockade Plus Interferon-Γ Add-On Antifungal Therapy in the Treatment of Refractory Covid-Associated Pulmonary Aspergillosis and Cerebral Mucormycosis

Cited by 15 publications

References 24 publications

Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

Relationship Between Corona Virus Infection And Immune Checkpoint Inhibitors

Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading

Contact Info

Product

Resources

About