Cited by 1,058Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesCancer Genomics and Diagnostics

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Natural selection of tumor variants in the generation of “tumor escape” phenotypes

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Khong, Hung T., Restifo, Nicholas P.·2002·Nature Immunology

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Abstract

The idea that tumors must "escape" from immune recognition contains the implicit assumption that tumors can be destroyed by immune responses either spontaneously or as the result of immunotherapeutic intervention. Simply put, there is no need for tumor escape without immunological pressure. Here, we review evidence supporting the immune escape hypothesis and critically explore the mechanisms that may allow such escape to occur. We discuss the idea that the central engine for generating immunoresistant tumor cell variants is the genomic instability and dysregulation that is characteristic of the transformed genome. "Natural selection" of heterogeneous tumor cells results in the survival and proliferation of variants that happen to possess genetic and epigenetic traits that facilitate their growth and immune evasion. Tumor escape variants are likely to emerge after treatment with increasingly effective immunotherapies.

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Authors: Khong, H. T., & Restifo, N. P.
Affiliations: National Institutes of Health (US)
Corresponding author: Khong, Hung T.
Restifo, Nicholas P.
ORCID: Khong, Hung T.
Restifo, Nicholas P.
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2002-11
Volume: 3
Issue: 11
Pages: 999-1005
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni1102-999
PMC: PMC1508168
OpenAlex: W2051940153
Cited by: 1,058
References: 104
Citations by year: 2026: 17 · 2025: 18 · 2024: 33 · 2023: 45 · 2022: 35 · 2021: 28 · 2020: 40 · 2019: 39 · 2018: 38 · 2017: 51 · 2016: 32 · 2015: 43 · 2014: 41 · 2013: 63 · 2012: 44
FWCI: 5.47
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
University of Regensburg Publication Server (University of Regensburg)
Funders: National Institutes of Health (Z99 CA999999)
National Cancer Institute (Z01BC010763)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords: tumor immune evasion, natural selection, tumor heterogeneity, tumor variants, genomic instability, immunoresistance, epigenetic regulation, cancer immunotherapy resistance, immune evasion
MeSH terms: Animals, Antigens, Neoplasm, HLA Antigens, Humans, Immunologic Surveillance, Immunotherapy, Killer Cells, Natural, Neoplasms, Selection, Genetic, T-Lymphocytes, Cytotoxic, Immunodominant Epitopes, Cytokines, Apoptosis, Models, Immunological, Disease Progression, Tumor Escape, T-Lymphocytes, Regulatory, Mice

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Natural selection of tumor variants in the generation of “tumor escape” phenotypes

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