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Background: In patients with metastatic triple-negative breast cancer (TNBC), programmed death-ligand 1 (PD-L1) expression has been demonstrated to predict response to immunotherapy. It is unclear whether PD-L1 expression measured with currently available validated assays can predict chemotherapy response in patients with non-metastatic TNBC.
Methods: We conducted a systematic review and meta-analysis of clinical studies to assess the PD-L1 expression as a predictor of response to chemotherapy in non-metastatic TNBC using validated assays. The primary endpoint was pathological complete response (pCR) rate to neoadjuvant chemotherapy. Secondary endpoints included the prevalence of PD-L1 expression in non-metastatic TNBC and its impact on disease-free survival (DFS) and overall survival (OS). Moreover, RNA sequence data from the TCGA breast cancer cohort was used to define the relationship between expression and response to chemotherapy and prognosis.
Results: Nineteen studies were eligible for the meta-analysis with a total of 2403 patients with non-metastatic TNBC disease. The PD-L1-positive cohort had a significantly higher likelihood of achieving pCR with neoadjuvant chemotherapy (pooled odds ratio = 1.95; 95% CI = 1.39-2.73, < 0.0001). In studies which reported long-term outcomes, PD-L1 positivity was associated with significantly better DFS and OS compared to PD-L1 negative patients (pooled hazard ratio = 0.51; 95% CI = 0.35-0.74, < 0.0001 and 0.51; 95% CI = 0.27-0.94, = 0.031, respectively). Transcriptomic data suggested that PD-L1 expression is a surrogate marker for the upregulation of key immune-related genes that mediate response to chemotherapy in TNBC.
Conclusion: This analysis clearly shows that patients with PD-L1 positive TNBC respond better to neoadjuvant chemotherapy and are associated with better survival outcomes compared to patients with PD-L1 negative tumours. The newly distinct quadruple negative breast cancer (QNBC) subtype should be defined as the BC subtype with the poorest outcome in the non-metastatic setting, highlighting the need for more aggressive therapy approaches.
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http://dx.doi.org/10.1080/1354750X.2022.2112614 | DOI Listing |
Front Immunol
September 2025
Department of Thoracic Surgery, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, China.
Background: Lung cancer remains the leading cause of cancer-related mortality globally, primarily due to late-stage diagnosis, molecular heterogeneity, and therapy resistance. Key biomarkers such as EGFR, ALK, KRAS, and PD-1 have revolutionized precision oncology; however, comprehensive structural and clinical validation of these targets is crucial to enhance therapeutic efficacy.
Methods: Protein sequences for EGFR, ALK, KRAS, and PD-1 were retrieved from UniProt and modeled using SWISS-MODEL to generate high-confidence 3D structures.
Front Immunol
September 2025
Precision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Gliomas are the most common primary malignant tumors of the central nervous system (CNS), and despite progress in molecular diagnostics and targeted therapies, their prognosis remains poor. In recent years, immunotherapy has emerged as a promising treatment modality in cancer therapy. However, the inevitable immune evasion by tumor cells is a key barrier affecting therapeutic efficacy.
View Article and Find Full Text PDFAm J Transplant
September 2025
Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School; Department of Surgery, Massachusetts General Hospital, Harvard Medical School; Department of Surgery, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania
Achieving immune tolerance is a key goal in organ transplantation, as it eliminates the need for long-term immunosuppression. Regulatory B cells (Bregs) present a promising strategy for inducing tolerance. Our previous findings demonstrate that the adoptive transfer of ex vivo-expanded murine splenic B regulatory cells, referred to as TLR-Bregs (TLR9/TLR4 stimulation), induces tolerance to allografts.
View Article and Find Full Text PDFCell Rep Med
September 2025
Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. Electronic address:
The success of immune checkpoint inhibitors is limited by multiple factors, including poor T cell infiltration and function within tumors, partly due to a dense extracellular matrix (ECM). Here, we investigate modulating the ECM by targeting integrin α5β1, a major fibronectin-binding and organizing integrin, to improve immunotherapy outcomes. Use of a function-blocking murinized α5β1 antibody reduces fibronectin fibril formation, enhances CD8 T cell transendothelial migration, increases vascular permeability, and decreases vessel-associated collagen.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2025
State Key Laboratory of Medicinal Chemical Biology and College of Life Science, Nankai University, Tianjin, China. Electronic address:
Oncolytic viruses (OVs) represent a promising approach for cancer immunotherapy by inducing direct tumor lysis and stimulating antitumor immunity. However, tumor-intrinsic resistance remains a major barrier to their efficacy. In this study, we established an OV-resistant MC38 colon cancer model (MC38) and identified interferon regulatory factor 7 (IRF7), a key regulator of type I interferon signaling, as significantly upregulated in resistant cells.
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