American Association for Cancer Research
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10780432ccr193685-sup-232157_3_supp_6507999_qf97y2.pptx (133.18 kB)

Supplementary fig 17 from Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer

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posted on 2023-03-31, 22:14 authored by Margaret L. Axelrod, Mellissa J. Nixon, Paula I. Gonzalez-Ericsson, Riley E. Bergman, Mark A. Pilkinton, Wyatt J. McDonnell, Violeta Sanchez, Susan R. Opalenik, Sherene Loi, Jing Zhou, Sean Mackay, Brent N. Rexer, Vandana G. Abramson, Valerie M. Jansen, Simon Mallal, Joshua Donaldson, Sara M. Tolaney, Ian E. Krop, Ana C. Garrido-Castro, Jonathan D. Marotti, Kevin Shee, Todd W. Miller, Melinda E. Sanders, Ingrid A. Mayer, Roberto Salgado, Justin M. Balko

Supplementary Figure 17: An 8-gene activated T cell signature derived from whole blood at surgery is associated with residual disease burden and recurrence.

Funding

Susan G. Komen

NIH

NCI

Department of Defense Era of Hope

Vanderbilt-Ingram Cancer Center

Dartmouth College Norris Cotton Cancer Center

History

ARTICLE ABSTRACT

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). 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. 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. 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.