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High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types
Open accessAbstract
Background High tumor mutation burden (TMB-H) has been proposed as a predictive biomarker for response to immune checkpoint blockade (ICB), largely due to the potential for tumor mutations to generate immunogenic neoantigens. Despite recent pan-cancer approval of ICB treatment for any TMB-H tumor, as assessed by the targeted FoundationOne CDx assay in nine tumor types, the utility of this biomarker has not been fully demonstrated across all cancers. Patients and methods Data from over 10 000 patient tumors included in The Cancer Genome Atlas were used to compare approaches to determine TMB and identify the correlation between predicted neoantigen load and CD8 T cells. Association of TMB with ICB treatment outcomes was analyzed by both objective response rates (ORRs, N = 1551) and overall survival (OS, N = 1936). Results In cancer types where CD8 T-cell levels positively correlated with neoantigen load, such as melanoma, lung, and bladder cancers, TMB-H tumors exhibited a 39.8% ORR to ICB [95% confidence interval (CI) 34.9-44.8], which was significantly higher than that observed in low TMB (TMB-L) tumors [odds ratio (OR) = 4.1, 95% CI 2.9-5.8, P < 2 × 10 −16 ]. In cancer types that showed no relationship between CD8 T-cell levels and neoantigen load, such as breast cancer, prostate cancer, and glioma, TMB-H tumors failed to achieve a 20% ORR (ORR = 15.3%, 95% CI 9.2-23.4, P = 0.95), and exhibited a significantly lower ORR relative to TMB-L tumors (OR = 0.46, 95% CI 0.24-0.88, P = 0.02). Bulk ORRs were not significantly different between the two categories of tumors ( P = 0.10) for patient cohorts assessed. Equivalent results were obtained by analyzing OS and by treating TMB as a continuous variable. Conclusions Our analysis failed to support application of TMB-H as a biomarker for treatment with ICB in all solid cancer types. Further tumor type-specific studies are warranted.
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Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Siegel, R. L., Miller, K. D., & Jemal, A. (2020) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21590 · Cited by 20,444
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
The Immune Landscape of Cancer
Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Ou Yang, T.-H., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.023 · Cited by 5,870
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
Mariathasan, S., Turley, S. J., Nickles, D., Castiglioni, A., Yuen, K., Wang, Y., Kadel III, E. E., Koeppen, H., Astarita, J. L., Cubas, R., et al. (2018) · Nature · doi:10.1038/nature25501 · Cited by 5,400
Tumor mutational load predicts survival after immunotherapy across multiple cancer types
Samstein, R. M., Lee, C.-H., Shoushtari, A. N., Hellmann, M. D., Shen, R., Janjigian, Y. Y., Barron, D. A., Zehir, A., Jordan, E. J., Omuro, A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0312-8 · Cited by 4,071
Molecular and genetic properties of tumors associated with local immune cytolytic activity
Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G., & Hacohen, N. (2015) · Cell · doi:10.1016/j.cell.2014.12.033 · Cited by 3,825
Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma
Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., Berent-Maoz, B., Pang, J., Chmielowski, B., Cherry, G., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.065 · Cited by 3,448
Zehir, A., Benayed, R., Shah, R. H., Syed, A., Middha, S., Kim, H. R., Srinivasan, P., Gao, J., Chakravarty, D., Devlin, S. M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4333 · Cited by 3,380
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Marcus, L., Fashoyin-Aje, L. A., Donoghue, M., Yuan, M., Rodriguez, L., Gallagher, P. S., Philip, R., Ghosh, S., Theoret, M. R., Beaver, J. A., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0327 · Cited by 578
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Zhang, J., Huang, D., Saw, P. E., & Song, E. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.04.010 · Cited by 534
Precision treatment in advanced hepatocellular carcinoma
Yang, X., Yang, C., Zhang, S., Geng, H., Zhu, A. X., Bernards, R., Qin, W., Fan, J., Wang, C., & Gao, Q. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.01.007 · Cited by 429
Targeting the DNA damage response in immuno-oncology: developments and opportunities
Chabanon, R. M., Rouanne, M., Lord, C. J., Soria, J.-C., Pasero, P., & Postel-Vinay, S. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-021-00386-6 · Cited by 293
Metadata
- Authors
- McGrail, D. J., Pilié, P. G., Rashid, N. U., Voorwerk, L., Slagter, M., Kok, M., Jonasch, E., Khasraw, M., Heimberger, A. B., Lim, B., Ueno, N. T., Litton, J. K., Ferrarotto, R., Chang, J. T., Moulder, S. L., & Lin, S.-Y.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 32
- Issue
- 5
- Pages
- 661-672
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W3136653115
- Cited by
- 1,032
- References
- 18
- FWCI
- 64.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- McGrail, D. J., Pilié, P. G., Rashid, N. U., Voorwerk, L., Slagter, M., Kok, M., Jonasch, E., Khasraw, M., Heimberger, A. B., Lim, B., Ueno, N. T., Litton, J. K., Ferrarotto, R., Chang, J. T., Moulder, S. L., & Lin, S.-Y. (2021). High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types. Annals of Oncology. https://doi.org/10.1016/j.annonc.2021.02.006
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