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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]
Experimental — accuracy not yet measuredIn the citing paper
“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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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
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