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Neoadjuvant chemotherapy (NACT), introduced in 1970 for inoperable tumors, has become the standard treatment approach in locally advanced breast cancer (LABC). Pathological complete response (pCR) following NACT is an important indicator for disease-free survival. An increased number of CD8-positive tumor-infiltrating lymphocytes (TILs) in the tumor center is thought to indicate an effective antitumor-immune response. Aberrant expression of programmed death ligand-1 (PD-L1) allows tumor cells to escape the host immune system. Change in PD-L1 expression may serve as an indirect indicator to assess the response to NACT. The residual cancer burden (RCB) category defined by routine histopathological evaluation represents the extent of residual disease and may predict disease-free survival. In this study, we assessed the expression of PD-L1 and CD8 in pre- and post-NACT specimens and their role in predicting pathological response to NACT. This study was conducted for a period of 3 years at Uttar Pradesh University of Medical Sciences, Saifai. PD-L1 and CD8 expression was compared on pre- and post-NACT tissue specimens. Pathological response to NACT was assessed by the RCB system. A total of 62 cases were evaluated. The mean age of patients was 47.58 ± 11.16 years. Six (9.7%) patients achieved pCR (RCB-0). PD-L1 and CD8 expression was found to be positively associated with pathological response ( < 0.001 for both). Tumors with negative PD-L1 (OR = 0.02) and pre-NACT intermediate/low expression of CD8 in TILs (OR = 0.11) are less likely to show a response to NACT. Prognostic role of PD-L1 and CD8 was also assessed by the Nottingham prognostic index (NPI) The expression of PD-L1 and CD8-positive TILs correlate with response to chemotherapy. High PD-L1 and CD8-positive TILs may predict better response to neoadjuvant chemotherapy.
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http://dx.doi.org/10.1007/s13193-024-02139-x | DOI Listing |
Cell 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.
View Article and Find Full Text PDFJ Clin Invest
September 2025
State Key Laboratory of Molecular Oncology, National Cancer Center/National, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Pancreatic cancer (PC) is notoriously resistant to both chemotherapy and immunotherapy, presenting a major therapeutic challenge. Epigenetic modifications play a critical role in PC progression, yet their contribution to chemoimmunotherapy resistance remains poorly understood. Here, we identified the transcription factor ZEB1 as a critical driver of chemoimmunotherapy resistance in PC.
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Background: Peltopepimut-S is a therapeutic vaccine, which induces specific expansion of both CD4+helper and CD8+cytotoxic T-cells against human papillomavirus type 16 (HPV16) E6/E7 oncoproteins.
Patients And Methods: In a randomized phase 2 trial, we evaluated the efficacy and safety of peltopepimut-S plus cemiplimab compared with cemiplimab alone as first-line or second-line therapy in recurrent/metastatic HPV16-positive head and neck cancer. The primary efficacy endpoint was the objective response rate (ORR) by an independent review (Response Evaluation Criteria in Solid Tumors version 1.
PLoS Pathog
September 2025
School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Zika virus (ZIKV) has emerged as a rising concern in global health in recent years. The role of PD-1/PD-L1 immune checkpoint in acute ZIKV infection remains to be understood. In this study we demonstrated the activation of PD-1/PD-L1 immune checkpoint by ZIKV.
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