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 language | English (US) |
|---|---|
| Article number | 2171 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
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ASJC Scopus subject areas
- General
Cite this
Contraction of T cell richness in lung cancer brain metastases. / Mansfield, Aaron; Ren, Hongzheng; Sutor, Shari; Sarangi, Vivekananda; Nair, Asha; Davila, Jaime; Elsbernd, Laura R.; Udell, Julia B.; Dronca, Roxana S; Park, Sean S; Markovic, Svetomir Nenad; Sun, Zhifu D; Halling, Kevin C.; Nevala, Wendy K.; Aubry, Marie Christine; Dong, Haidong M; Jen, Jin.
In: Scientific Reports, Vol. 8, No. 1, 2171, 01.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Contraction of T cell richness in lung cancer brain metastases
AU - Mansfield, Aaron
AU - Ren, Hongzheng
AU - Sutor, Shari
AU - Sarangi, Vivekananda
AU - Nair, Asha
AU - Davila, Jaime
AU - Elsbernd, Laura R.
AU - Udell, Julia B.
AU - Dronca, Roxana S
AU - Park, Sean S
AU - Markovic, Svetomir Nenad
AU - Sun, Zhifu D
AU - Halling, Kevin C.
AU - Nevala, Wendy K.
AU - Aubry, Marie Christine
AU - Dong, Haidong M
AU - Jen, Jin
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041592072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041592072&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-20622-8
DO - 10.1038/s41598-018-20622-8
M3 - Article
C2 - 29391594
AN - SCOPUS:85041592072
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 2171
ER -