Lien, Huang‐Chun
Mayo Clinic
National Taiwan University Hospital
Citations 2
Antigen-Presenting B-Cell Signature Predicts Response and Survival in HER2-Positive Breast Cancer
Ku, Wen‐Hui, Lin, Chia-Jen, Wu, Bogang, Wu, H. , Yen, Tzu‐Chun, Lo, Chiao , Wang, Ming-Yang, Huang, Chiun-Sheng, Lin, Po‐Han , Lien, Huang‐Chun , Tsai, Li‐Wei , Wang, Ming-Yang, Kuo, Sung‐Hsin , Huang, Chiun‐Sheng
No container title available | May 12, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Neoadjuvant therapy (NAT) with HER2-targeted agents is the standard treatment for patients with HER2-positive early breast cancer (HER2 + EBC). Although high levels of tumor-infiltrating lymphocytes (TILs) are associated with higher pathologic complete response (pCR) rates and improved recurrence-free survival (RFS), the specific immune components responsible remain unclear. In this study, pretreatment tumor biopsies from 188 patients receiving HER2-targeted NAT were analyzed. Univariate analysis revealed that enrichment of TIL-B cells in tumors, high HER2 mRNA and low ESR1 mRNA expression were linked to pCR (both p < 0.01). Multivariate analysis confirmed TIL-B-cell enrichment as an independent predictor of pCR. Mature IgD/IgM-high B cells, but not immature RAG1 + B cells, independently predicted pCR. Transcriptomic profiling identified 265 upregulated genes in pCR tumors enriched in MHC class II antigen presentation pathways. Immunofluorescence demonstrated increased spatial interaction of mature B cells with CD4 + T cells in pCR tumors, consistent with active antigen presentation. The antigen presenting B-cell signature, integrated mature B-cell and MHC II profile, was the strongest independent predictor of pCR (OR = 3.008, 95% CI: 1.196–7.544, p = 0.019) and was also significantly associated with improved RFS (HR = 0.109, 95% CI: 0.014–0.872), highlighting B-cell–mediated antigen presentation as a clinically relevant biomarker in HER2 + EBC.
The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice
González-Ericsson, Paula I. , Stovgaard, Elisabeth Specht , Reisenbichler, Emily , Kos, Zuzana , Carter, Jodi M. , Michiels, Stefan , Quesne, John Le , Lænkholm, Anne‐Vibeke , Adam, Julien , Bartlett, John MS, Rimm, David L. , Quinn, Cecily , Cree, Ian A. , Hida, Akira I. , Haynes, Harry R. , Frahm, Isabel, Acosta‐Haab, Gabriela, Balancin, Marcelo Luiz , Bellolio, Enrique , Yang, Wentao , Kirtani, Pawan , Sugie, Tomoharu , Ehinger, Anna , Castaneda, Carlos, Kok, Marleen , McArthur, Heather L. , Siziopikou, Kalliopi P. , Fineberg, Susan , Gown, Allen M. , Viale, Giuseppe , Schnitt, Stuart J. , Pruneri, Giancarlo , Penault‐Llorca, Frederique, Hewitt, Stephen M. , Thompson, E. Aubrey , Allison, Kimberly H. , Symmans, W. Fraser , Bellizzi, Andrew M. , Brogi, Edi , Moore, David A. , Larsimont, Denis , Dillon, Deborah , Broeckx, Glenn , Bairi, Khalid El , Cimino‐Mathews, Ashley , Adams, Sylvia , Liu, S, Loibl, Sibylle , Chen, I‐Chun , Juco, Jonathan, Blackley, Elizabeth F. , Demaria, Sandra , Leon‐Ferre, Roberto A. , Zardavas, Dimitrios, Emancipator, Kenneth , Ely, Scott , Loi, Sherene , Salgado, Roberto , Group, International Immuno‐Oncology Biomarker Working, Cree, Ian , Haynes, Harry R , Balancin, Marcelo , Ehinger, Anna , Lazar, Alexander J , Broeckx, Glenn , El Bairi, Khalid , Leon-Ferre, Roberto, Gonzalez-Ericsson, Paula I , Bellizzi, Andrew M , Symmans, W Fraser , Loi, Sherene , Pruneri, Giancarlo , Rimm, David , Carter, Jodi , Sua, Luz Fernanda , Nielsen, Torsten O. , Fox, Stephen B. , Bartlett, John MS, Peeters, Dieter J. E. , Dieci, Maria Vittoria , Vincent‐Salomon, Anne , Balko, Justin M. , Badve, Sunil , Penault-Llorca, Frederique Madeleine , Lazar, Alexander J. , Lien, Huang‐Chun , Goetz, Matthew P. , Harbeck, Nadia , Sotiriou, Christos P. , Lakhani, Sunil R. , Denkert, Carsten , Gluz, Oleg , Sanders, Melinda E. , Group, International Immuno‐Oncology Biomarker Working
The Journal of Pathology | March 4, 2020 | Volume: 250 | Issue: 5 | Pages: 667-684
AbstractImmune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.