RT Journal Article
SR Electronic
T1 Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 5668
OP 5681
DO 10.1158/1078-0432.CCR-19-3685
VO 26
IS 21
A1 Axelrod, Margaret L.
A1 Nixon, Mellissa J.
A1 Gonzalez-Ericsson, Paula I.
A1 Bergman, Riley E.
A1 Pilkinton, Mark A.
A1 McDonnell, Wyatt J.
A1 Sanchez, Violeta
A1 Opalenik, Susan R.
A1 Loi, Sherene
A1 Zhou, Jing
A1 Mackay, Sean
A1 Rexer, Brent N.
A1 Abramson, Vandana G.
A1 Jansen, Valerie M.
A1 Mallal, Simon
A1 Donaldson, Joshua
A1 Tolaney, Sara M.
A1 Krop, Ian E.
A1 Garrido-Castro, Ana C.
A1 Marotti, Jonathan D.
A1 Shee, Kevin
A1 Miller, Todd W.
A1 Sanders, Melinda E.
A1 Mayer, Ingrid A.
A1 Salgado, Roberto
A1 Balko, Justin M.
YR 2020
UL http://clincancerres.aacrjournals.org/content/26/21/5668.abstract
AB Purpose: The recent approval of anti-programmed death-ligand 1 immunotherapy in combination with nab-paclitaxel for metastatic triple-negative breast cancer (TNBC) highlights the need to understand the role of chemotherapy in modulating the tumor immune microenvironment (TIME).Experimental Design: We examined immune-related gene expression patterns before and after neoadjuvant chemotherapy (NAC) in a series of 83 breast tumors, including 44 TNBCs, from patients with residual disease (RD). Changes in gene expression patterns in the TIME were tested for association with recurrence-free (RFS) and overall survival (OS). In addition, we sought to characterize the systemic effects of NAC through single-cell analysis (RNAseq and cytokine secretion) of programmed death-1–high (PD-1HI) CD8+ peripheral T cells and examination of a cytolytic gene signature in whole blood.Results: In non-TNBC, no change in expression of any single gene was associated with RFS or OS, while in TNBC upregulation of multiple immune-related genes and gene sets were associated with improved long-term outcome. High cytotoxic T-cell signatures present in the peripheral blood of patients with breast cancer at surgery were associated with persistent disease and recurrence, suggesting active antitumor immunity that may indicate ongoing disease burden.Conclusions: We have characterized the effects of NAC on the TIME, finding that TNBC is uniquely sensitive to the immunologic effects of NAC, and local increases in immune genes/sets are associated with improved outcomes. However, expression of cytotoxic genes in the peripheral blood, as opposed to the TIME, may be a minimally invasive biomarker of persistent micrometastatic disease ultimately leading to recurrence.This article is featured in Highlights of This Issue, p. 5541