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Tumour burden and efficacy of immune-checkpoint inhibitors

Abstract

Accumulating evidence suggests that a high tumour burden has a negative effect on anticancer immunity. The concept of tumour burden, simply defined as the total amount of cancer in the body, in contrast to molecular tumour burden, is often poorly understood by the wider medical community; nonetheless, a possible role exists in defining the optimal treatment strategy for many patients. Historically, tumour burden has been assessed using imaging. In particular, CT scans have been used to evaluate both the number and size of metastases as well as the number of organs involved. These methods are now often complemented by metabolic tumour burden, measured using the more recently developed 2-deoxy-2-[18F]-fluoro-d-glucose (FDG)-PET/CT. Serum-based biomarkers, such as lactate dehydrogenase, can also reflect tumour burden and are often also correlated with a poor response to immune-checkpoint inhibitors. Other circulating markers (such as circulating free tumour DNA and/or circulating tumour cells) are also attracting research interest as surrogate markers of tumour burden. In this Review, we summarize evidence supporting the utility of tumour burden as a biomarker to guide the use of immune-checkpoint inhibitors. We also describe data and provide perspective on the various tools used for tumour burden assessment, with a particular emphasis on future therapeutic strategies that might address the issue of inferior outcomes among patients with cancer with a high tumour burden.

Key points

  • The search for predictive biomarkers of responsiveness to immune-checkpoint inhibitors (ICIs) remains an active area of research.

  • Tumour burden can be assessed using imaging, liquid biopsy methods or through the quantification of biological tumour derivatives such as lactate dehydrogenase or serum-based biomarkers.

  • Accumulating evidence supports a prognostic role for tumour burden in patients receiving ICIs.

  • The detrimental effects of tumour burden on the efficacy of ICIs probably reflect differences in tumour biology relative to lower-burden disease.

  • Further investigations are warranted to distinguish between the prognostic and potentially predictive validity of tumour burden in patients receiving ICIs.

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Fig. 1: Measuring tumour burden.
Fig. 2: A summary of preclinical evidence of a detrimental effect of tumour burden on anticancer immunity.

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Acknowledgements

We wish to acknowledge Dr Stephan De Botton of the Département d’Hématologie, Gustave Roussy Cancer Campus, Villejuif, France, for his help in revising this manuscript.

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F.G.D., C.C., N.C. and B.B. researched data for this article. All authors made a substantial contribution to discussions of content. F.G.D. and B.B. wrote the manuscript. All authors reviewed and/or edited the manuscript prior to submission.

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Correspondence to Benjamin Besse.

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A.M. has acted as an adviser and/or consultant of Amgen, AstraZeneca/Medimmune, BMS, GSK, IMCheck, J&J, Merck (MSD), Merck Serono, OSE immunotherapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Sanofi and Symphogen/Servier, has received travel support from AstraZeneca, BMS, Merck (MSD) and Roche, and has received research funding from BMS, Boehringer Ingelheim, Fondation MSD Avenir, Merus and Transgene. C.C. has acted as a consultant of AstraZeneca, BMS, MSD and Roche. N.C. has received research funding from AstraZeneca, BMS Foundation, Cytune pharma, GSK and Roche. C.R. has acted as a consultant of Amgen, BMS, MSD, Novartis, Pfizer, Pierre Fabre, Roche and Sanofi. B.B. has conducted research funded by Abbvie, Amgen, Aptitude Health, AstraZeneca, Beigene, Biogen, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Ignyta, Inivata, Ipsen, Merck, MSD, Nektar, Onxeo, OSE immunotherapeutics, Pfizer, Pharma Mar, Roche-Genentech, Sanofi, Spectrum Pharmaceuticals, Takeda,Tiziana Pharm 4D Pharma and Tolero Pharmaceuticals.

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Nature Reviews Clinical Oncology thanks Richard Joseph, Michael Sorich and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Dall’Olio, F.G., Marabelle, A., Caramella, C. et al. Tumour burden and efficacy of immune-checkpoint inhibitors. Nat Rev Clin Oncol (2021). https://doi.org/10.1038/s41571-021-00564-3

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