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Updated: Sep 27, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Dynamic Changes in PD-L1, VEGF, and TILs Following Neoadjuvant Therapy in Residual Invasive Breast Cancer
Marina Bakula1,2, Jasmina Rajc1,2, Ana Kvolik Pavic2,3
1Clinical Institute of Pathology and Forensic Medicine, University Hospital Center Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia.
Background/Objectives:
Neoadjuvant therapy (NAT) may remodel the breast-cancer microenvironment. We evaluated paired changes in programmed death-ligand 1 (PD-L1), vascular endothelial growth factor (VEGF), and tumor-infiltrating lymphocytes (TILs) before and after NAT, and associations with the residual cancer burden (RCB) and survival.
Methods:
This retrospective study included 102 patients with residual invasive breast cancer after NAT: 34 with luminal B-like/HER2-negative, 34 with luminal B-like/HER2-positive, and 34 with triple-negative breast cancer (TNBC). PD-L1 was assessed using the 22C3 combined positive score, VEGF by the cytoplasmic staining intensity, and stromal TILs according to international recommendations.
Results:
The median tumor size decreased from 2.5 to 1.7 cm (p < 0.001), the PD-L1 CPS (combined positive score) from 6 to 5 (p = 0.039), and the TILs from 15% to 10% (p < 0.001), whereas VEGF shifted toward stronger staining (p = 0.03). In TNBC, the PD-L1 CPS decreased from 10 to 5 (p = 0.003) and the TILs from 20% to 8% (p < 0.001). Biomarkers were not associated with the RCB in the overall cohort. The initial tumor size predicted RCB II/III (OR: 2.60, p = 0.038). The overall survival differed by subtype (p < 0.001).
Conclusions:
NAT has induced subtype-dependent immune and angiogenic changes, supporting biomarker reassessment in residual disease.
