Immune Checkpoint Inhibitors and Hypertension: A Scoping Review

Objectives Immune mechanisms are recognized contributors to hypertension, and previous studies have proposed that hypertension may have an autoimmune basis.[1,2] Immune checkpoint inhibitors (ICIs), widely used as immunotherapies across diverse malignancies, have been increasingly reported to cause autoimmune-related adverse effects. In this scoping review, we tested the hypothesis that ICIs may precipitate hypertension through immune-mediated mechanisms.

Methods A scoping review evaluating the incidence of hypertension in patients receiving ICIs, either as monotherapy or in combination with other anticancer agents, was conducted in accordance with the Joanna Briggs Institute (JBI) methodology and the PRISMA-ScR reporting guidelines. A comprehensive search of PubMed, CINAHL, Embase, and MEDLINE databases was performed for studies published up to June 30, 2025. Eligible studies included adults (≥18 years) with cancer treated with programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, excluding those with pre-existing hypertension. We identified ICI drug classes, combination regimens, and cancer types that are most frequently associated with hypertension.

Results A total of 200 studies (n = 226 incidence values) were included in this review. The reported median participant age ranged from 30 to 79 years among patients receiving ICIs in combination with other anticancer agents, and from 54 to 70 years among those treated with ICI monotherapy. The incidence of hypertension demonstrated considerable heterogeneity across studies, with a median of 28.6% (range 0.0-100%) in the combination therapy group (n = 211) and 8.2% (range 0.0-54.3%) in the monotherapy group (n = 15) (Figure 1). Hypertensive events were most reported with PD-1 inhibitors, followed by PD-L1 inhibitors, while CTLA-4 inhibitors demonstrated the lowest reported frequency. Notably, the occurrence of hypertension was more pronounced in combination regimens, particularly those including tyrosine kinase inhibitors (TKIs) or vascular endothelial growth factors (VEGF) inhibitors. Among cancer types, hepatocellular carcinoma and lung cancer were most frequently associated with hypertension in the ICI combination and monotherapy groups, respectively.

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Figure 1.

Incidence of Hypertension across ICI-based regimens

Conclusion Our findings demonstrate that ICIs, especially in combination therapy, increases the occurrence of hypertension in cancer patients, suggesting the importance of immune mechanisms in the development of hypertension. Given the limited number of studies characterizing hypertension arising from ICIs, further research is warranted to elucidate underlying mechanisms, refine risk stratification, and inform evidence-based clinical decision-making.

References [1.] Cohen Tervaert JW. Hypertension Res 2011;34:443-4. [2.] Pober JS. J Clin Invest 2014;124:4234-6.