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Updated: Sep 11, 2025

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Role of immunosuppressive JNK pathway in the tumor microenvironment among TNBC subtypes in IBCSG trial 22-00
Andrea Joaquin Garcia1, Takashi Semba2,3,4, Mattia Rediti1,5
1Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Abstract:
Phosphorylation of the JNK (pJNK) protein promotes an immunosuppressive tumor microenvironment (TME), enhancing aggressiveness in inflammatory triple-negative breast cancer (TNBC). This study evaluated the role of JNK signaling using a gene signature. RNA sequencing was performed on 347 TNBC tumors from the phase 3 International Breast Cancer Study Group (IBCSG) 22-00 trial, which evaluated adjuvant low-dose cyclophosphamide and methotrexate (CM). Immune-related tumors were identified by TNBC subtype or tumor-infiltrating lymphocytes (TILs). Associations between JNK and outcomes were analyzed using Cox models. Low pJNK levels were associated with better disease-free survival (DFS) in immune-related tumors. These tumors also had lower Treg levels and higher CD8+/Treg ratios. Notably, immunomodulatory (IM) tumors with high pJNK showed improved DFS when treated with CM. High pJNK expression identifies immunosuppressive TMEs with poor prognosis in inflamed TNBC. However, these tumors may benefit from CM, supporting pJNK as a potential biomarker for immunotherapy strategies.
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