ArticlePloS one2021
Hydroxychloroquine (HCQ) decreases the benefit of anti-PD-1 immune checkpoint blockade in tumor immunotherapy.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.Immunology · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Targeting Autophagy to Overcome Chemoresistance and Immune Resistance in Triple-Negative Breast Cancer.Cancers · 2026Review
- The impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors.Nature reviews. Cancer · 2026Review
- Immune checkpoint inhibitor associated lichenoid eruptions: a review of non-steroidal systemic maintenance therapies.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Review
- Targeting autophagy to enhance cancer immunotherapy: emerging mechanisms and strategies.Medical oncology (Northwood, London, England) · 2025Review
- Autophagy inhibition improves the efficacy of anlotinib and PD-1 inhibitors in the treatment of NSCLC.Journal for immunotherapy of cancer · 2025Article
- Review
- Decreased progenitor TCF1 + T-cells correlate with COVID-19 disease severity.Communications biology · 2024Article
- Safety of Immunomodulatory Systemic Therapies Used in the Management of Immune-Related Cutaneous Adverse Events.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Immunosuppression for immune-related adverse events during checkpoint inhibition: an intricate balance.NPJ precision oncology · 2023Review
- Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.Journal of hematology & oncology · 2022Review
- Monitoring and Management of the Patient with Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis: Current Perspectives.Journal of inflammation research · 2022Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapy using checkpoint blockade (ICB) with antibodies such as anti-PD-1 has revolutionised the treatment of many cancers. Despite its use to treat COVID-19 patients and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, the effect of hydroxychloroquine (HCQ) on cancer immunotherapy has not been examined. In this study, remarkably, we find that HCQ alone, or in combination with azithromycin (AZ), at doses used to treat patients, decreased the therapeutic benefit of anti-PD-1 in cancer immunotherapy. No deleterious effect was seen on untreated tumors. Mechanistically, HCQ and HCQ/AZ inhibited PD-L1 expression on tumor cells, while specifically targeting the anti-PD-1 induced increase in progenitor CD8+CD44+PD-1+TCF1+ tumor infiltrating T cells (TILs) and the generation of CD8+CD44+PD-1+ effectors. Surprisingly, it also impaired the appearance of a subset of terminally exhausted CD8+ TILs. No effect was seen on the presence of CD4+ T cells, FoxP3+ regulatory T cells (Tregs), thymic subsets, B cells, antibody production, myeloid cells, or the vasculature of mice. This study indicates for the first time that HCQ and HCQ/AZ negatively impact the ability of anti-PD-1 checkpoint blockade to promote tumor rejection.
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