Immune interactions in pembrolizumab (PD-1 inhibitor) cancer therapy and cardiovascular complications

Am J Physiol Heart Circ Physiol. 2023 Oct 1;325(4):H751-H767. doi: 10.1152/ajpheart.00378.2023. Epub 2023 Aug 18.

Abstract

The use of immunotherapies like pembrolizumab (PEM) is increasingly common for the management of numerous cancer types. The use of PEM to bolster T-cell response against tumor growth is well documented. However, the interactions PEM has on other immune cells to facilitate tumor regression and clearance is unknown and warrants further investigation. In this review, we present literature findings that have reported the interactions of PEM in stimulating innate and adaptive immune cells, which enhance cytotoxic phenotypes. This triggers secretion of cytokines and chemokines, which have both beneficial and detrimental effects. We also describe how this leads to the development of rare but underreported occurrence of PEM-induced immune-related cardiovascular complications that arise suddenly and progress rapidly to debilitating and fatal consequences. This review encourages further research and investigation of PEM-induced cardiovascular complications and other immune cell interactions in patients with cancer. As PEM therapy in treating cancer types is expanding, we expect that this review will inform health care professionals of diverse specializations of medicine like dermatology (melanoma skin cancers), ophthalmology (eye cancers), and pathology (hematological malignancies) about PEM-induced cardiac complications.

Keywords: anti-cancer drug; cardiac toxicity; clinical monitoring; immune modulation; inflammation; myocarditis; targeted therapy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Melanoma*
  • Skin Neoplasms*

Substances

  • Immune Checkpoint Inhibitors
  • pembrolizumab
  • Antibodies, Monoclonal, Humanized