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Immune phenotype and response to neoadjuvant systemic therapy (NAST) in triple negative breast cancer (TNBC)

Authors :
Gaiane M. Rauch
Haven R. Garber
Edwin Roger Parra Cuentas
Er-Yen Yen
Gheath Alatrash
Clinton Yam
Anne V. Philips
Sahil Seth
Gabriel N. Hortobagyi
Xiangjie Sun
Roland L. Bassett
Fei Yang
Senthil Damodaran
Jason B White
Jennifer A. Wargo
Lei Huo
Elizabeth A. Mittendorf
Stacy L. Moulder
Jennifer K. Litton
William Fraser Symmans
Source :
Journal of Clinical Oncology. 38:509-509
Publication Year :
2020
Publisher :
American Society of Clinical Oncology (ASCO), 2020.

Abstract

509 Background: In TNBC patients (pts) receiving NAST, increasing tumor infiltrating lymphocytes (TILs) is associated with higher pathologic complete response (pCR) rates. However, since the presence of TIL do not consistently predict pCR, the current study was undertaken to more fully characterize the immune cell response and its association with pCR. Methods: T cell receptor (TCR) sequencing, PD-L1 immunohistochemistry and multiplex immunofluorescence were performed on prospectively collected pre-NAST tumor samples from 98 pts with stage I-III TNBC enrolled in ARTEMIS (NCT: 02276443). TCR clonality was calculated using Shannon’s entropy. PD-L1+ was defined as ≥1% immune cell staining. Response to NAST was defined using the residual cancer burden (RCB) index. Associations between TCR clonality, immune phenotype, and response were examined with the Wilcoxon rank sum test, Spearman’s rank correlation and multivariable logistic regression using stepwise elimination (threshold p > 0.2), as appropriate. Results: The pCR rate was 39% (38/98). pCR was associated with higher TCR clonality (median = 0.2 [in pts with pCR] vs 0.1 [in pts with residual disease], p = 0.05). Notably, the association between pCR and higher TCR clonality was observed in pts with ≥5% TIL (n = 61; p = 0.05) but not in pts with < 5% TIL (n = 37; p = 0.87). Among pts with ≥5% TIL, TCR clonality emerged as the only independent predictor of response in a multivariable model of tumor immune characteristics (odds ratio/0.1 increase in TCR clonality: 3.0, p = 0.021). PD-L1+ status was associated with higher TCR clonality (median = 0.2 [in PD-L1+] vs 0.1 [in PD-L1-], p = 0.004). Higher TCR clonality was associated with higher CD3+ (rho = 0.32, p = 0.0018) and CD3+CD8+ (rho = 0.33, p = 0.0013) infiltration but lower expression of PD-1 on CD3+ (rho = -0.24, p = 0.021) and CD3+CD8+ cells (rho = -0.21, p = 0.037). Conclusions: In TNBC, a more clonal T cell population is associated with an immunologically active microenvironment (higher CD3+ and CD3/8+ T cell; lower PD-1+CD3+ and PD-1+CD3/8+ T cell; PD-L1+) and favorable response to NAST, especially in pts with ≥5% TIL, suggesting a role for deep immune phenotyping in further refining the predictive value of TILs.

Details

ISSN :
15277755 and 0732183X
Volume :
38
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi...........7a70eab6aeae1749f2df35178fa21023
Full Text :
https://doi.org/10.1200/jco.2020.38.15_suppl.509