Cited by 1,192Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesCancer Genomics and Diagnostics

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The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker

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Jardim, Denis L., Goodman, Aaron, de Melo Gagliato, Debora, Kurzrock, Razelle·2021·Cancer Cell

DOI 10.1016/j.ccell.2020.10.001PMC PMC7878292

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Abstract

Tumor mutational burden (TMB) reflects cancer mutation quantity. Mutations are processed to neo-antigens and presented by major histocompatibility complex (MHC) proteins to T cells. To evade immune eradication, cancers exploit checkpoints that dampen T cell reactivity. Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enabling T cell reactivation; however, response biomarkers are required, as most patients do not benefit. Higher TMB results in more neo-antigens, increasing chances for T cell recognition, and clinically correlates with better ICI outcomes. Nevertheless, TMB is an imperfect response biomarker. A composite predictor that also includes critical variables, such as MHC and T cell receptor repertoire, is needed.

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Authors: Jardim, D. L., Goodman, A., de Melo Gagliato, D., & Kurzrock, R.
Affiliations: Hospital Sírio-Libanês (BR)
University of California San Diego (US)
Corresponding author: Kurzrock, Razelle
ORCID: Jardim, Denis L.
Goodman, Aaron
Kurzrock, Razelle
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2021-02
Volume: 39
Issue: 2
Pages: 154-173
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccell.2020.10.001
PMC: PMC7878292
OpenAlex: W3097803258
Cited by: 1,192
References: 151
Citations by year: 2026: 134 · 2025: 263 · 2024: 294 · 2023: 276 · 2022: 171 · 2021: 53
FWCI: 13.60
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 372 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Astellas Pharma US
National Cancer Institute (P30 CA023100)
Janssen Pharmaceuticals
AstraZeneca
Bristol-Myers Squibb
Genentech
Roche
EMD Serono
Pfizer
Meso Scale Diagnostics
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 mutational burden, immunotherapy biomarkers, immune checkpoint inhibitors, neoantigens, MHC class I antigen presentation, T cell receptor repertoire, cancer immunotherapy response prediction
MeSH terms: Immune Checkpoint Inhibitors, Humans, Immunotherapy, Major Histocompatibility Complex, Mutation, Neoplasms, T-Lymphocytes, Biomarkers, Tumor

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The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker

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