The DOI matches its Crossref record; 96 of the 97 references it cites were found in a registry or an index.
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 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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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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Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
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Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
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The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
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Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157
Cancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198
Cited by
Sorted by citations
Hallmarks of response, resistance, and toxicity to immune checkpoint blockade
Morad, G., Helmink, B. A., Sharma, P., & Wargo, J. A. (2021) · Cell · doi:10.1016/j.cell.2021.09.020 · Cited by 1,648
Immune-related adverse events of checkpoint inhibitors
Ramos‐Casals, M., Brahmer, J. R., Callahan, M. K., Flores-Chávez, A., Keegan, N. M., Khamashta, M. A., Lambotte, O., Mariette, X., Prat, A., & Suarez-Almazor, M. E. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-0160-6 · Cited by 1,491
Lv, M., Chen, M., Zhang, R., Zhang, W., Wang, C., Zhang, Y., Wei, X., Guan, Y., Liu, J., Feng, K., et al. (2020) · Cell Research · doi:10.1038/s41422-020-00395-4 · Cited by 1,040
Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends
Sun, Q., Hong, Z., Zhang, C., Wang, L., Han, Z., & Ma, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01522-4 · Cited by 598
ImmunoPET: Concept, Design, and Applications
Wei, W., Rosenkrans, Z. T., Liu, J., Huang, G., Luo, Q., & Cai, W. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00738 · Cited by 504
Metadata
- 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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