Neoadjuvant Interferons: Critical for Effective PD-1–Based Immunotherapy in TNBC
Academic Article
-
- Overview
-
- Research
-
- Identity
-
- Additional Document Info
-
- View All
-
Overview
abstract
-
The lack of targeted therapies available for triple-negative breast cancer (TNBC) patients who fail to respond to first-line chemotherapy has sparked interest in immunotherapeutic approaches. However, trials utilizing checkpoint inhibitors targeting the PD-1/PD-L1 axis in TNBC have had underwhelming responses. Here, we investigated the interplay between type I IFN signaling and the PD-1/PD-L1 axis and tested the impact of combining IFN inducers, as immune activators, with anti-PD-1, to induce an antimetastatic immune response. Using models of TNBC, we demonstrated an interplay between type I IFN signaling and tumor cell PD-L1 expression that affected therapeutic response. The data revealed that the type I IFN-inducer poly(I:C) was an effective immune activator and antimetastatic agent, functioning better than anti-PD-1, which was ineffective as a single agent. Poly(I:C) treatment induced PD-L1 expression on TNBC cells, and combined poly(I:C) and anti-PD-1 treatment prolonged metastasis-free survival in a neoadjuvant setting via the induction of a tumor-specific T-cell response. Use of this combination in a late treatment setting did not impact metastasis-free survival, indicating that timing was critical for immunotherapeutic benefit. Together, these data demonstrated anti-PD-1 as an ineffective single agent in preclinical models of TNBC. However, type I IFN inducers were effective immune activators, and neoadjuvant trials combining them with anti-PD-1 to induce a sustained antitumor immune response are warranted. Cancer Immunol Res; 5(10); 871-84. ©2017 AACR.
status
publication date
has subject area
published in
Research
keywords
-
ANTITUMOR FUNCTION
-
BREAST-CANCER METASTASIS
-
EXPRESSION
-
I INTERFERONS
-
IMMUNE ESCAPE
-
Immunology
-
Life Sciences & Biomedicine
-
MELANOMA PATIENTS
-
Oncology
-
PD-1 PATHWAY
-
POLYADENYLIC-POLYURIDYLIC ACID
-
RANDOMIZED-TRIAL
-
Science & Technology
-
TUMOR-INFILTRATING LYMPHOCYTES
Identity
Digital Object Identifier (DOI)
PubMed ID
Additional Document Info
Publisher
-
American Association for Cancer Research
start page
end page
volume
issue