A guide to cancer immunotherapy: from T cell basic science to clinical practice

Waldman, Alex D.; Fritz, Jill M.; Lenardo, Michael J.

doi:10.1038/s41577-020-0306-5

Cited by 4,154Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

A guide to cancer immunotherapy: from T cell basic science to clinical practice

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Waldman, Alex D., Fritz, Jill M., Lenardo, Michael J.·2020·Nature Reviews Immunology

DOI 10.1038/s41577-020-0306-5PMC PMC7238960

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Abstract

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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Myeloid-specific HIF-1α overexpression produces hyperinflammatory, M1-polarized macrophages with increased glycolysis, suggesting a link between HIF-1α and M1 polarization.
“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]
The cited review’s PD1/PDL1 biological function section discusses glucose uptake in T cells, and its adoptive T cell transfer section discusses macrophage-mediated inflammation. Neither passage addresses myeloid-specific HIF-1α overexpression, M1 polarization, or increased macrophage glycolysis. Searches for those terms and HIF-1α found no passage supporting the attributed claim. (LLM, conf=0.76)
Experimental — accuracy not yet measured
The possible contribution of the adaptive immune system in AD patients to reducing cancer incidence has not been studied.
“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]
The Introduction discusses cancer immunosurveillance and reports melanoma regression in patients with concomitant autoimmune disease, but it does not address whether adaptive immunity in AD patients contributes to lower cancer incidence or whether that question has been studied. Searches for Alzheimer disease and atopic dermatitis alongside cancer incidence found no passage addressing the claim. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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.
“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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Authors: Waldman, A. D., Fritz, J. M., & Lenardo, M. J.
Affiliations: National Institutes of Health (US)
Corresponding author: Lenardo, Michael J.
ORCID: Waldman, Alex D.
Fritz, Jill M.
Lenardo, Michael J.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2020-05-20
Volume: 20
Issue: 11
Pages: 651-668
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/s41577-020-0306-5
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 · 2015: 1 · 2014: 1
FWCI: 58.00
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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A guide to cancer immunotherapy: from T cell basic science to clinical practice

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