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A guide to cancer immunotherapy: from T cell basic science to clinical practice
Open accessAbstract
The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy.
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“Conversely, myeloid-specific overexpression of HIF-1α results in hyperinflammatory, M1-polarized macrophages associated with increased glycolysis, suggesting a link between HIF-1α and M1-polarization [63].”
From Revisiting the HIF switch in the tumor and its immune microenvironment. (2022) · cites this paper as [63]
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“The possible contribution of the adaptive immune system in AD patients to reducing cancer incidence has not been studied (4,5).”
From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [5]
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“Typically, PD‐L1 or PD‐L2 are expressed on the surface of cancer cells or antigen‐presenting cells and transduce a signal for cooperation with PD‐1 expression on the cell surface of T lymphocytes to stimulate restraint signaling [272, 273].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [272]
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Self-citationPredicting Tumor Response to PD-1 Blockade
Ding, L., & Chen, F. (2019) · New England Journal of Medicine · doi:10.1056/nejmcibr1906340 · Cited by 34
Expression of CTLA‐4 and FOXP3 in cis protects from lethal lymphoproliferative disease
Chikuma, S., & Bluestone, J. A. (2007) · European Journal of Immunology · doi:10.1002/eji.200737159 · Cited by 32
Tolcher, A. W., Alley, E. W., Chichili, G. R., Baughman, J. E., Moore, P. A., Bonvini, E., Vasselli, J. R., Wigginton, J. M., & Powderly, J. D. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.tps3105 · Cited by 27
Jure‐Kunkel, M., Masters, G. R., Girit, E., Dito, G., & Lee, F. Y. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.3048 · Cited by 20
The Era of Checkpoint Blockade in Lung Cancer: Taking the Brakes Off the Immune System
Moon, E. K., Langer, C. J., & Albelda, S. Μ. (2017) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201702-152fr · Cited by 20
Flagged first, then by citations
2 of the 302 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Therapeutic Targeting of the Tumor Microenvironment
Bejarano, L., Jordão, M. J. C., & Joyce, J. A. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1808 · Cited by 1,718
Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion
Jhunjhunwala, S., Hammer, C., & Delamarre, L. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00339-z · Cited by 1,570
Clinical and therapeutic relevance of cancer-associated fibroblasts
Chen, Y., McAndrews, K. M., & Kalluri, R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00546-5 · Cited by 1,230
Gerstberger, S. C., Jiang, Q., & Ganesh, K. (2023) · Cell · doi:10.1016/j.cell.2023.03.003 · Cited by 1,010
Nanomedicine in cancer therapy
Fan, D., Cao, Y., Cao, M., Wang, Y., Cao, Y., & Gong, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01536-y · Cited by 986
Metadata
- Authors
- Waldman, A. D., Fritz, J. M., & Lenardo, M. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lenardo, Michael J.
- Venue
- Nature Reviews Immunology
- Published
- 2020-05-20
- Volume
- 20
- Issue
- 11
- Pages
- 651-668
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC7238960
- OpenAlex
- W3028523516
- Cited by
- 4,154
- References
- 302
- Citations by year
- 2026: 382 · 2025: 748 · 2024: 867 · 2023: 824 · 2022: 754 · 2021: 511 · 2020: 59
- FWCI
- 58.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Emory University
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM008169)
- National Institute of Allergy and Infectious Diseases
- NHLBI Division of Intramural Research
- 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, T cells, T cell regulation, immune checkpoint blockade, adoptive cellular therapy, clinical trials, immunotherapy toxicity, history of cancer immunotherapy
- MeSH terms
- Immune Checkpoint Inhibitors, Animals, Clinical Trials as Topic, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Immunotherapy, Adoptive, Cancer Vaccines
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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