ArticleThe Journal of clinical investigation2021
Early reduction in PD-L1 expression predicts faster treatment response in human cutaneous leishmaniasis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Lymphocyte-mediated immune responses to Leishmania infection.Nature reviews. Immunology · 2026Review
- Spatial mapping of Ethiopian cutaneous leishmaniasis lesions reveals distinct tissue level immune programs.Frontiers in immunology · 2026Article
- Leishmaniasis.Nature reviews. Disease primers · 2025Review
- Leishmania amazonensis infection induces PD-L1 expression on dendritic cells and impairs Th1 responses in vitro and in vivo.Scientific reports · 2025Article
- IL-32-producing CD8+ memory T cells define immunoregulatory niches in human cutaneous leishmaniasis.The Journal of clinical investigation · 2025Article
- A randomized, double-blind phase 2b trial to evaluate efficacy of ChAd63-KH for treatment of post kala-azar dermal leishmaniasis.Molecular therapy. Methods & clinical development · 2024Article
- Evaluation of Less Invasive Sampling Tools for the Diagnosis of Cutaneous Leishmaniasis.Open forum infectious diseases · 2024Article
- Intralesional gene expression profile of JAK-STAT signaling pathway and associated cytokines inFrontiers in immunology · 2024Article
- Characterisation of tumor microenvironment and prevalence of CD274/PD-L1 genetic alterations difference in colorectal Cancer.BMC cancer · 2023Article
- Visceral Leishmaniasis and the Skin: Dermal Parasite Transmission to Sand Flies.Pathogens (Basel, Switzerland) · 2022Review
- Excretory/secretory proteins inhibit host immune responses by downregulating the TLR4/NF-κB/MAPKs signaling pathway: A possible mechanism of immune evasion in parasitic nematodeFrontiers in immunology · 2022Article
- Overcoming roadblocks in the development of vaccines for leishmaniasis.Expert review of vaccines · 2021Review
- Spatially Resolved Immunometabolism to Understand Infectious Disease Progression.Frontiers in microbiology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
Abstract
Cutaneous leishmaniasis (CL) is caused by Leishmania donovani in Sri Lanka. Pentavalent antimonials (e.g., sodium stibogluconate [SSG]) remain first-line drugs for CL with no new effective treatments emerging. We studied whole blood and lesion transcriptomes from Sri Lankan patients with CL at presentation and during SSG treatment. From lesions but not whole blood, we identified differential expression of immune-related genes, including immune checkpoint molecules, after onset of treatment. Using spatial profiling and RNA-FISH, we confirmed reduced expression of programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) proteins on treatment in lesions of a second validation cohort and further demonstrated significantly higher expression of these checkpoint molecules on parasite-infected compared with noninfected lesional CD68+ monocytes and macrophages. Crucially, early reduction in PD-L1 but not IDO1 expression was predictive of rate of clinical cure (HR = 4.88) and occurred in parallel with reduction in parasite load. Our data support a model whereby the initial anti-leishmanial activity of antimonial drugs alleviates checkpoint inhibition on T cells, facilitating immune-drug synergism and clinical cure. Our findings demonstrate that PD-L1 expression can be used as a predictor of rapidity of clinical response to SSG treatment in Sri Lanka and support further evaluation of PD-L1 as a host-directed therapeutic in leishmaniasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.