Adverse Events Following Cancer Immunotherapy: Obstacles and Opportunities
Open accessAbstract
Oncology has recently undergone a revolutionary change with widespread adoption of immunotherapy for many cancers. Immunotherapy using monoclonal antibodies against checkpoint molecules, including programmed death (PD)-1, PD ligand (PD-L)1, and cytotoxic T lymphocyte-associated antigen (CTLA)-4, is effective in a significant subset of patients. However, immune-related adverse events (irAEs) have emerged as frequent complications of checkpoint blockade, likely due to the physiological role of checkpoint pathways in regulating adaptive immunity and preventing autoimmunity. As immunotherapy becomes more common, a better understanding of the etiology of irAEs and ways to limit these events is needed. At the same time, studying these new therapy-related disorders provides an opportunity to better understand naturally occurring human autoimmune and inflammatory disorders, with the potential to improve therapies for cancer and autoimmune diseases.
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The organ systems affected, severity, and timing of immune-related adverse events vary between anti-CTLA-4 and anti-PD-1/PD-L1 agents and their combinations.
“The breadth of systems affected, severity and timing of irAEs can all vary between agents, specifically between anti-CTLA-4 agents and anti-PD-1/PD-L1 and combinations thereof”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Pauken et al., 2019
Immune-related adverse events are common: low-grade events occur in more than 90% of patients, and severe events occur in 20-60%.
“irAEs are common, with a low-grade (Grade 1-2) effect observed in up to more than 90% of patients, while more severe effects (Grades 3-5) can range from 20-60%”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Pauken et al., 2019
Immune-related adverse events include over 70 pathologies affecting nearly every organ system.
“irAEs comprise over 70 different pathologies affecting nearly every organ system including the neurologic, genitourinary, gastrointestinal, pulmonary, cardiovascular, and integumentary systems”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Pauken et al., 2019
The onset of immune-related adverse events varies widely, from days to weeks to months after therapy.
“the onset of irAE varies widely with some starting days to weeks after therapy and others months”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Pauken et al., 2019
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- Authors
- Pauken, K. E., Dougan, M., Rose, N. R., Lichtman, A. H., & Sharpe, A. H.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Lichtman, Andrew H.
- Sharpe, Arlene H.
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 40
- Issue
- 6
- Pages
- 511-523
- ISSN
- 1471-4906 (ISSN-L)
- PMC
- PMC6527345
- OpenAlex
- W2943668434
- Cited by
- 280
- References
- 97
- Citations by year
- 2026: 24 · 2025: 33 · 2024: 43 · 2023: 46 · 2022: 42 · 2021: 37 · 2020: 40 · 2019: 15
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Trends in Immunology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- US National Institutes of Health Mentored Clinical Scientist Development Award (1K08DK114563-01)
- American Gastroenterological Association Research Scholars Award (HL121363, HL13186)
- National Institutes of Health (R01 AI040614, P01 AI056299, AI108545)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- immune-related adverse events, cancer immunotherapy, immune checkpoint blockade, PD-1, PD-L1, CTLA-4, monoclonal antibodies, autoimmunity, autoimmune disease therapy
- MeSH terms
- Antineoplastic Agents, Immunological, Animals, Disease Susceptibility, Humans, Immunotherapy, Neoplasms, Biomarkers, Tumor, Autoimmunity, T-Lymphocyte Subsets, Disease Management, Immunomodulation, Tumor Microenvironment, Patient Outcome Assessment
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