Contraction of T cell richness in lung cancer brain metastases

Aaron Mansfield, Hongzheng Ren, Shari Sutor, Vivekananda Sarangi, Asha Nair, Jaime Davila, Laura R. Elsbernd, Julia B. Udell, Roxana S Dronca, Sean S Park, Svetomir Nenad Markovic, Zhifu D Sun, Kevin C. Halling, Wendy K. Nevala, Marie Christine Aubry, Haidong M Dong, Jin Jen

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24 Scopus citations

Abstract

Very little is known about how the adaptive immune system responds to clonal evolution and tumor heterogeneity in non-small cell lung cancer. We profiled the T-cell receptor β complementarity determining region 3 in 20 patients with fully resected non-small cell lung cancer primary lesions and paired brain metastases. We characterized the richness, abundance and overlap of T cell clones between pairs, in addition to the tumor mutation burden and predicted neoantigens. We found a significant contraction in the number of unique T cell clones in brain metastases compared to paired primary cancers. The vast majority of T cell clones were specific to a single lesion, and there was minimal overlap in T cell clones between paired lesions. Despite the contraction in the number of T cell clones, brain metastases had higher non-synonymous mutation burdens than primary lesions. Our results suggest that there is greater richness of T cell clones in primary lung cancers than their paired metastases despite the higher mutation burden observed in metastatic lesions. These results may have implications for immunotherapy.

Original languageEnglish (US)
Article number2171
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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    Mansfield, A., Ren, H., Sutor, S., Sarangi, V., Nair, A., Davila, J., Elsbernd, L. R., Udell, J. B., Dronca, R. S., Park, S. S., Markovic, S. N., Sun, Z. D., Halling, K. C., Nevala, W. K., Aubry, M. C., Dong, H. M., & Jen, J. (2018). Contraction of T cell richness in lung cancer brain metastases. Scientific Reports, 8(1), [2171]. https://doi.org/10.1038/s41598-018-20622-8