Application of Immune Checkpoint Inhibitors in Cancer

Abstract

Cancer is a significant challenge to society and public health in the 21st century. According to GLOBOCAN 2020, there were 19.3 million new cancer cases with approximately 10.0 million deaths in 2020 globally. By 2040, 28 million new cases and 16.2 million deaths are estimated. With the escalating challenges of cancer and limitations of conventional therapies like surgery, chemotherapy, and radiotherapy, the development of novel therapies such as immunotherapy and targeted therapy is required. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has become a significant advancement in cancer treatment, combating tumors by activating the immune system. This review offers a thorough overview of ICIs, including their classification, mechanisms of action, and adverse events. It also examines the application of ICIs across various cancer types especially on advanced or unresectable malignancies, such as head and neck squamous cell carcinoma, esophageal cancer, non-small cell lung cancer, breast cancer, hepatocellular carcinoma, and bladder cancer, highlighting their therapeutic potential and the challenges they face. By providing a comprehensive analysis, this review aims to construct a reference system for clinicians to better understand and utilize ICIs in treating cancer.

Keywords: Advanced malignancies; Adverse events; Clinical application; Immune checkpoint inhibitors; Immune checkpoints.

FIGURE 1

Therapeutic landscape of immune checkpoint inhibitors in diverse cancers. [Created with the Generic Diagramming Platform (GDP, https://BioGDP.com).] This figure summarizes the regulatory approvals of immune checkpoint inhibitors (ICIs) for head and neck squamous cell carcinoma (HNSCC), esophageal cancer (EC), non‐small cell lung cancer (NSCLC), triple‐negative breast cancer (TNBC), hepatocellular carcinoma (HCC), and urothelial carcinoma (UC). The timeline highlights drug names, approval dates, pivotal clinical trials, and indications (including PD‐L1 expression thresholds and prior therapy requirements). This figure is sourced from the official website of the US Food and Drug Administration (US FDA).

FIGURE 2

The organ‐specific toxicity atlas of immune‐related adverse events. (The figure is redrawn from Figure 2 in Chen et al.’s article [224], originally published under a CC BY 4.0 license.) This figure systematically categorizes organ‐specific immune‐related adverse events (irAEs) associated with immune checkpoint inhibitor therapy. The atlas classifies irAEs by affected organ systems, including central nervous system (encephalitis, meningitis, cerebritis, hypophysitis), respiratory system (pneumonitis, sarcoidosis), liver (hepatitis), skin (rash, vitiligo, psoriasis, SJS/TEN), endocrine system (hyperthyroidism, thyroiditis), cardiovascular system (myocarditis, pericarditis, vasculitis, MACES), gastrointestinal system (diarrhea, enterocolitis), and musculoskeletal system (arthritis, arthralgia). Abbreviations: ATG, antithymocyte globulin; MACEs, major adverse cardiac events; SJS, Stevens–Johnson syndrome; TEN, toxic epidermal necrolysis.