Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer.
Adult
Aged
Albumins
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
B7-H1 Antigen
/ antagonists & inhibitors
CD8-Positive T-Lymphocytes
/ drug effects
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Lymphocytes, Tumor-Infiltrating
/ drug effects
Middle Aged
Neoadjuvant Therapy
/ adverse effects
Neoplasm Proteins
/ genetics
Neoplasm Recurrence, Local
/ drug therapy
Paclitaxel
/ administration & dosage
Prognosis
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Progression-Free Survival
Treatment Outcome
Triple Negative Breast Neoplasms
/ drug therapy
Tumor Microenvironment
/ drug effects
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 11 2020
01 11 2020
Historique:
received:
12
11
2019
revised:
21
05
2020
accepted:
18
08
2020
pubmed:
23
8
2020
medline:
27
11
2021
entrez:
23
8
2020
Statut:
ppublish
Résumé
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-1 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.
Identifiants
pubmed: 32826327
pii: 1078-0432.CCR-19-3685
doi: 10.1158/1078-0432.CCR-19-3685
pmc: PMC7642197
mid: NIHMS1623537
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
B7-H1 Antigen
0
CD274 protein, human
0
Neoplasm Proteins
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5668-5681Subventions
Organisme : NCI NIH HHS
ID : R01 CA200994
Pays : United States
Organisme : NIH HHS
ID : S10 OD016355
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA090625
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA236157
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023108
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA098131
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007347
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA181491
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA216966
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211869
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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