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The status of tumor mutational burden and immunotherapy

Nature Cancer volume 3, pages 652–656 (2022)Cite this article

Tumor mutational burden (TMB) has received significant attention within ongoing pursuits of biomarkers of response to immune checkpoint inhibitors, and notably received FDA approval as a companion diagnostic biomarker for pembrolizumab. Here, four experts discuss the utility, challenges, and open questions surrounding TMB in the context of cancer immunotherapy.

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References

  1. Marabelle, A. et al. J. Clin. Oncol. 38, 1–10 (2020).

    Article  CAS  Google Scholar 

  2. Valero, C. et al. JAMA Oncol. 7, 739–743 (2021).

    Article  Google Scholar 

  3. Samstein, R. M. et al. Nat. Genet. 51, 202–206 (2019).

    Article  CAS  Google Scholar 

  4. Rousseau, B. et al. N. Engl. J. Med. 384, 1168–1170 (2021).

    Article  Google Scholar 

  5. Rizvi, N. A. et al. Science 348, 124–128 (2015).

    Article  CAS  Google Scholar 

  6. McGranahan, N. et al. Science 351, 1463–1469 (2016).

    Article  CAS  Google Scholar 

  7. Anagnostou, V. et al. Nat. Cancer 1, 99–111 (2020).

    Article  CAS  Google Scholar 

  8. Alspach, E. et al. Nature 574, 696–701 (2019).

    Article  CAS  Google Scholar 

  9. Anagnostou, V. et al. Cell Rep. Med. 1, 100139 (2020).

    Article  Google Scholar 

  10. Litchfield, K. et al. Cell 184, 596–614.e514 (2021).

    Article  CAS  Google Scholar 

  11. Gubin, M. M. et al. Nature 515, 577–581 (2014).

    Article  CAS  Google Scholar 

  12. Amodio, V. et al. Cancers 13, 2638 (2021).

    Article  CAS  Google Scholar 

  13. Bassani-Sternberg, M. et al. Nat. Commun. 7, 13404 (2016).

    Article  CAS  Google Scholar 

  14. Yang, W. et al. Nat. Med. 25, 767–775 (2019).

    Article  CAS  Google Scholar 

  15. Oka, M. et al. Genome Biol. 22, 9 (2021).

    Article  CAS  Google Scholar 

  16. Iyer, J. G. et al. Clin. Cancer Res. 17, 6671–6680 (2011).

    Article  CAS  Google Scholar 

  17. Vega, D. M. et al. Ann. Oncol. https://doi.org/10.1016/j.annonc.2021.09.016 (2021).

    Article  PubMed  Google Scholar 

  18. Budczies, J. et al. Ann. Oncol. 30, 1496–1506 (2019).

    Article  CAS  Google Scholar 

  19. Siravegna, G. et al. Cancer Cell 34, 148–162 (2018).

    Article  CAS  Google Scholar 

  20. Si, H. et al. Clin. Cancer Res. 27, 1631–1640 (2021).

    Article  CAS  Google Scholar 

  21. Litchfield, K. et al. Cell Rep. 31, 107550 (2020).

    Article  CAS  Google Scholar 

  22. Zhou, K. I. et al. Clin. Cancer Res. 26, 6453–6463 (2020).

    Article  CAS  Google Scholar 

  23. Chowell, D. et al. Nat. Biotechnol. 40, 499–506 (2022).

    Article  CAS  Google Scholar 

  24. Rozeman, E. A. et al. Nat. Med. 27, 256–263 (2021).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Valsamo Anagnostou

  2. Department of Oncology, University of Torino, Candiolo, TO, Italy

    Alberto Bardelli

  3. Candiolo Cancer Institute, FPO - IRCCS, Candiolo, TO, Italy

    Alberto Bardelli

  4. Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, Cleveland, OH, USA

    Timothy A. Chan

  5. National Center for Regenerative Medicine, Case Comprehensive Cancer Center, Cleveland, OH, USA

    Timothy A. Chan

  6. Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK

    Samra Turajlic

  7. Skin and Renal Units, The Royal Marsden NHS Foundation Trust, London, UK

    Samra Turajlic

  8. Melanoma and Kidney Cancer Team, Institute of Cancer Research, London, UK

    Samra Turajlic

Authors
  1. Valsamo Anagnostou
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  2. Alberto Bardelli
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  3. Timothy A. Chan
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  4. Samra Turajlic
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Corresponding authors

Correspondence to Valsamo Anagnostou, Alberto Bardelli, Timothy A. Chan or Samra Turajlic.

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Competing interests

V.A. receives research funding (paid to Johns Hopkins University) from AstraZeneca and has received research funding (paid to Johns Hopkins University) from Bristol Myers Squibb in the past 5 years. A.B. has received grants/research support from Neophore, AstraZeneca, and Boehringer, as well as honoraria or consultation fees from Illumina, Guardant Health, and Inivata. A.B. is a stock shareholder in Neophore and has served on scientific advisory boards for Inivata, Neophore, and Roche/Genentech Global CRC Advisory Board. T.A.C. is a co-founder of Gritstone Oncology and holds equity. T.A.C. holds equity in NysnoBio. T.A.C. acknowledges grant funding from Bristol Myers Squibb, AstraZeneca, Illumina, Pfizer, InterVenn, An2H, and Eisai. T.A.C. has served as an advisor for Bristol-Myers, MedImmune, Squibb, Illumina, Eisai, AstraZeneca, and An2H. T.A.C. is an inventor on intellectual property held by MSKCC on using tumor mutation burden to predict immunotherapy response, with pending patent (62/569,053), which has been licensed to PGDx. S.T. is funded by Cancer Research UK (grant reference number A29911); the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC10988), the UK Medical Research Council (FC10988), and the Wellcome Trust (FC10988); the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (grant reference number A2204), Ventana Medical Systems Inc (grant reference numbers 10467 and 10530), the National Institute of Health ((U01 CA247439) and Melanoma Research Alliance (award ref. no 686061). S.T. has received speaking fees from Roche, AstraZeneca, Novartis and Ipsen. S.T. has the following patent filed: Indel mutations as a therapeutic target and predictive biomarker (PCTGB2018/051892).

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Anagnostou, V., Bardelli, A., Chan, T.A. et al. The status of tumor mutational burden and immunotherapy. Nat Cancer 3, 652–656 (2022). https://doi.org/10.1038/s43018-022-00382-1

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