Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy

Abstract

Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.

Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers

“…Innate immune cells could trigger the adaptive immune responses, and understanding of cancer-intrinsic processes will supply the exploration and development of immunotherapy ( 26 , 27 ). Cancer-associated fibroblast was reported to induce cancer cell proliferation, invasion, and metastasis through various pathways ( 28 , 29 ).…”

Clinical Patterns and Follow-Up of Inflammatory Arthritis and Other Immune-Related Adverse Events Induced by Checkpoint Inhibitors. A Multicenter Study

“…Treatment of rheumatic irAE is a challenge for clinicians, including rheumatologists and oncologists. The balance between risk and benefits should be individualized according to oncologic prognosis, ICI response, and severity of the irAE ( 29 ). The clinical scenario differs from the “classic” pattern that we usually see in inflammatory chronic arthritis and systemic rheumatic diseases, and many patients had a milder course with fewer requirements for GC or DMARDs ( 17 ).…”

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update

“…Thus, elucidation of the disease mechanisms underlying rheumatic irAEs may lead to novel therapeutic approaches for rheumatic diseases [ 61 ]. Although the precise mechanism remains unclear, ICIs block negative signals on activated T cells, leading to increased autoreactive T cells and inflammatory cytokines such as tumor necrosis factor-α (TNF-α), IL-6, and IL-17 [ 62 , 63 , 64 ]. This provides the rationale for targeted inhibition of these cytokines to treat rheumatic irAEs [ 65 , 66 ].…”

“…This provides the rationale for targeted inhibition of these cytokines to treat rheumatic irAEs [ 65 , 66 ]. ICIs can also induce epitope spreading, diversifying the epitope specificity of T cells [ 62 ]. Moreover, ICIs prevent the apoptosis of B cells, allowing for longer cell survival and increased autoantibody loads [ 62 ].…”