Deep sequencing of T-cell receptor DNA as a biomarker of clonally expanded TILs in breast cancer after immunotherapy Journal Article
| Authors: | Page, D. B.; Yuan, J.; Redmond, D.; Wen, Y. H.; Durack, J. C.; Emerson, R.; Solomon, S.; Dong, Z.; Wong, P.; Comstock, C.; Diab, A.; Sung, J.; Maybody, M.; Morris, E.; Brogi, E.; Morrow, M.; Sacchini, V.; Elemento, O.; Robins, H.; Patil, S.; Allison, J. P.; Wolchok, J. D.; Hudis, C.; Norton, L.; McArthur, H. L. |
| Article Title: | Deep sequencing of T-cell receptor DNA as a biomarker of clonally expanded TILs in breast cancer after immunotherapy |
| Abstract: | In early-stage breast cancer, the degree of tumor-infiltrating lymphocytes (TIL) predicts response to chemotherapy and overall survival. Combination immunotherapy with immune checkpoint antibody plus tumor cryoablation can induce lymphocytic infiltrates and improve survival in mice. We used T-cell receptor (TCR) DNA sequencing to evaluate both the effect of cryoimmunotherapy in humans and the feasibility of TCR sequencing in early-stage breast cancer. In a pilot clinical trial, 18 women with early-stage breast cancer were treated preoperatively with cryoablation, single-dose anti-CTLA-4 (ipilimumab), or cryoablation + ipilimumab. TCRs within serially collected peripheral blood and tumor tissue were sequenced. In baseline tumor tissues, T-cell density as measured by TCR sequencing correlated with TIL scores obtained by hematoxylin and eosin (H&E) staining. However, tumors with little or no lymphocytes by H&E contained up to 3.6 × 106 TCR DNA sequences, highlighting the sensitivity of the ImmunoSEQ platform. In this dataset, ipilimumab increased intratumoral T-cell density over time, whereas cryoablation ± ipilimumab diversified and remodeled the intratumoral T-cell clonal repertoire. Compared with monotherapy, cryoablation plus ipilimumab was associated with numerically greater numbers of peripheral blood and intratumoral T-cell clones expanding robustly following therapy. In conclusion, TCR sequencing correlates with H&E lymphocyte scoring and provides additional information on clonal diversity. These findings support further study of the use of TCR sequencing as a biomarker for T-cell responses to therapy and for the study of cryoimmunotherapy in early-stage breast cancer. © 2016 American Association for Cancer Research. |
| Journal Title: | Cancer Immunology Research |
| Volume: | 4 |
| Issue: | 10 |
| ISSN: | 2326-6066 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2016-10-01 |
| Start Page: | 835 |
| End Page: | 844 |
| Language: | English |
| DOI: | 10.1158/2326-6066.cir-16-0013 |
| PROVIDER: | scopus |
| PMCID: | PMC5064839 |
| PUBMED: | 27587469 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 December 2016 -- Source: Scopus |
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