Immunotherapeutic Strategies in Cancer and Atherosclerosis—Two Sides of the Same Coin

Abstract

The development and clinical approval of immunotherapies has revolutionized cancer therapy. Although the role of adaptive immunity in atherogenesis is now well-established and several immunomodulatory strategies have proven beneficial in preclinical studies, anti-atherosclerotic immunotherapies available for clinical application are not available. Considering that adaptive immune responses are critically involved in both carcinogenesis and atherogenesis, immunotherapeutic approaches for the treatment of cancer and atherosclerosis may exert undesirable but also desirable side effects on the other condition, respectively. For example, the high antineoplastic efficacy of immune checkpoint inhibitors, which enhance effector immune responses against tumor cells by blocking co-inhibitory molecules, was recently shown to be constrained by substantial proatherogenic properties. In this review, we outline the specific role of immune responses in the development of cancer and atherosclerosis. Furthermore, we delineate how current cancer immunotherapies affect atherogenesis and discuss whether anti-atherosclerotic immunotherapies may similarly have an impact on carcinogenesis.

Cardiovascular Complications of Pan-Cancer Therapies: The Need for Cardio-Oncology

“…T-cell-driven inflammation is vital to the emergence and progression of atherosclerosis [113,114]. Aberrant infiltration of CD4 + and CD8 + T cells in the vascular wall is closely associated with the formation of atherosclerotic lesions, which contribute to monopoiesis and macrophage accumulation as well as necrotic core formation in the early stages of atherosclerosis [113][114][115]. In fact, CD4 + T-cell subsets and their effector cytokines have distinct excitatory or inhibitory effects on both tumors and atherosclerosis [115].…”

“…Aberrant infiltration of CD4 + and CD8 + T cells in the vascular wall is closely associated with the formation of atherosclerotic lesions, which contribute to monopoiesis and macrophage accumulation as well as necrotic core formation in the early stages of atherosclerosis [113][114][115]. In fact, CD4 + T-cell subsets and their effector cytokines have distinct excitatory or inhibitory effects on both tumors and atherosclerosis [115]. Treatment with anti-PD-1 and anti-CTLA-4 antibodies reduced tumor burden but increased pro-inflammatory T-cell activation, leading to atherosclerosis progression.…”