Cancer immunotherapy using checkpoint blockade
Open accessAbstract
The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) or the programmed cell death 1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the preexistence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long-lasting disease control, yet one-third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon-γ signaling pathways. New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.
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Key roles of TGF-β1 in suppressing the adaptive immune system are apparent from the lymphoproliferative autoimmune phenotype of Tgfb1−/− mice and similar phenotypes following selective ablation of TGF-β signaling components within CD4+ and CD8+ T cells.
“Key roles of TGF-β1 in suppressing the adaptive immune system are apparent from the lymphoproliferative autoimmune phenotype of Tgfb1−/− mice197–199, and similar phenotypes following selective ablation of TGF-β signaling components within CD4+ and CD8+ T cells200.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [199]
ICI are proven effective in several solid and hematologic cancers.
“Immune checkpoint inhibitors (ICI) such as antibodies targeting CTLA-4, PD-1 and its ligand (PD-L1), are proven effective in several solid and hematologic cancers.1”
From <i>Faecalibacterium prausnitzii</i> strain EXL01 boosts efficacy of immune checkpoint inhibitors (2024) · cites this paper as [1]
Response rates to ICIs vary widely across cancers, from >80% in refractory Hodgkin's lymphoma to little or no response in mismatch repair-proficient colorectal cancer, with many indications at 20-40%.
“Response rates to ICI treatment vary widely among different cancers, ranging from greater than 80% in patients with refractory Hodgkin's lymphoma to little or no response in patients with mismatch repair-proficient colorectal cancer (76, 77); many tumor indications fall within a response rate range of 20% to 40% (78).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [78]
The overall survival response for immune checkpoint immunotherapies is not enough and needs more comprehensive study.
“Nonetheless, the overall survival response for these immunotherapies is not enough and needs a more comprehensive study [335].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [335]
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Ren, X., Guo, S., Guan, X., Kang, Y., Liu, J., & Yang, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.790113 · Cited by 62 · see citing works
Adverse events associated with immune checkpoint inhibitor treatment for cancer
Esfahani, K., Meti, N., Miller, W. H., & Hudson, M. (2019) · Canadian Medical Association Journal · doi:10.1503/cmaj.180870 · Cited by 65 · see citing works
McQuade, J. L., Ologun, G. O., Arora, R., & Wargo, J. A. (2020) · Current Oncology Reports · doi:10.1007/s11912-020-00913-y · Cited by 63 · see citing works
Cell Fate Reprogramming in the Era of Cancer Immunotherapy
Zimmermannova, O., Caiado, I., Ferreira, A. G., & Pereira, C.-F. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.714822 · Cited by 56 · see citing works
- Authors
- Ribas, A., & Wolchok, J. D.
- Affiliations
- University of California, Los Angeles (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Ribas, Antoni
- Wolchok, Jedd D.
- Venue
- Science
- Published
- 2018-03-23
- Volume
- 359
- Issue
- 6382
- Pages
- 1350-1355
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7391259
- OpenAlex
- W2791483720
- Cited by
- 6,791
- References
- 59
- Citations by year
- 2026: 734 · 2025: 827 · 2024: 928 · 2023: 899 · 2022: 963 · 2021: 905 · 2020: 787 · 2019: 576 · 2018: 166
- FWCI
- 63.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (R35 CA197633, P30 CA008748, P30 CA016042)
- Parker Institute for Cancer Immunotherapy (N/A)
- Ludwig Cancer Research (N/A)
- 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
- cancer immunotherapy, immune checkpoint blockade, CTLA-4, PD-1, antitumor T cells, acquired resistance, antigen presentation, interferon-gamma signaling, combination immunotherapy, tumor recurrence
- MeSH terms
- Antibodies, Humans, Immunotherapy, Neoplasms, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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