Early adjunct anti-PD-L1 immunotherapy improves outcomes and restores infection-induced immune paralysis in mice with invasive pulmonary mucormycosis. (PubMed, Proc Natl Acad Sci U S A) - May 21, 2026 - "Here, we performed sequential nCounter-based transcriptomics on lung tissue of cyclophosphamide-immunosuppressed mice with IPM (Rhizopus arrhizus infection) to dynamically study the pulmonary immune environment...For therapeutic studies, Mucorales-active antifungal therapy with isavuconazonium sulfate (ISAV) was initiated on day 3 after IPM infection, along with anti-PD-L1 or a nontargeting isotype antibody (control) given either on days 3 + 5 (early) or days 6 + 8 (late)...Notably, early adjunct anti-PD-L1 therapy promoted significantly stronger innate immune cell activation, upregulation of key cytokine pathways, reinvigoration of T-helper-cell signaling, and reversal of IPM-induced exhaustion signals than both late adjunct anti-PD-L1 and isotype control. These findings indicate that combined antifungal and early immunomodulatory therapy may be an important strategy to intercept immune paralysis and improve outcomes in immunocompromised hosts with IPM, inviting..."
IO biomarker • Journal • Preclinical • Infectious Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases
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Dimitrios P Kontoyiannis; Jezreel Pantaleón García; Lauren Matula; Nathaniel D Albert; Russell E Lewis; Scott E Evans; Sebastian Wurster; Uddalak Bharadwaj; Yongxing Wang
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