The DOI matches its Crossref record; 149 of the 151 references it cites were found in a registry or an index.
The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker
Open accessAbstract
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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“In certain tumour types, the number of neoantigens in a tumour (or tumour mutational burden (TMB)) is correlated with responsiveness to ICIs67,68.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [67]
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Cites
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Cited by
Sorted by citations
Cold and hot tumors: from molecular mechanisms to targeted therapy
Wu, B., Zhang, B., Li, B., Wu, H., & Jiang, M. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01979-x · Cited by 811
Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends
Sun, Q., Hong, Z., Zhang, C., Wang, L., Han, Z., & Ma, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01522-4 · Cited by 598
“However, TMB relies on the replication components and processes of the immune system to achieve this effect.(238) Mutated processes of leucocyte and T cell proliferation regulation are identified as better interpretable genomic predictors than TMB.”
BackgroundResistance Mechanisms to Anti-PD Cancer Immunotherapy
Vesely, M. D., Zhang, T., & Chen, L. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-070621-030155 · Cited by 468
Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma
Llovet, J. M., Pinyol, R., Yarchoan, M., Singal, A. G., Marron, T. U., Schwartz, M., Pikarsky, E., Kudo, M., & Finn, R. S. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00868-0 · Cited by 391
“In certain tumour types, the number of neoantigens in a tumour (or tumour mutational burden (TMB)) is correlated with responsiveness to ICIs 67,68 .”
Palmeri, M., Mehnert, J. M., Silk, A. W., Jabbour, S. K., Ganesan, S., Popli, P., Riedlinger, G., Stephenson, R. D., de Meritens, A. B., Leiser, A., et al. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100336 · Cited by 358
“Furthermore, in other histologies, such as Kaposi sarcoma(18) and Merkel cell carcinoma, response to ICIs has been shown in the absence of TMB-H.(21) These findings of responsiveness or nonresponsiveness to ICI independent of TMB status highlight that other factors affecting ICI”
BackgroundInfluential
Metadata
- 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
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 39
- Issue
- 2
- Pages
- 154-173
- ISSN
- 1535-6108 (ISSN-L)
- 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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