Characterization of the immune microenvironment in inflammatory breast cancer using multiplex immunofluorescence

Badr, Nahla M., McMurray, Jack L., Danial, Irini, Hayward, Steven, Asaad, Nancy Y., Abd El-Wahed, Moshira M., Abdou, Asmaa G., Serag El-Dien, Marwa M., Sharma, Nisha, Horimoto, Yoshiya, Sircar, Tapan, Vidya, Raghavan, Hoar, Fiona, Rea, Daniel, Jones, J. Louise, Stevens, Andrea, Spooner, David, Merard, Reena, Lewis, Paul, Hunter, Kelly John, Berditchevski, Fedor and Shaaban, Abeer M. (2023) Characterization of the immune microenvironment in inflammatory breast cancer using multiplex immunofluorescence. Pathobiology, 90 (1). 31–43. ISSN 1015-2008

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Introduction: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. Methods: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. Results: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. Conclusion: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.

Item Type: Article
Additional Information: Funding Information: Nahla M. Badr was funded by the Egyptian Mission Sector, The Ministry of Higher Education and Scientific Research, Egypt. Jack L. McMurray was funded by the CRUK studentship. Abeer M. Shaaban is funded by Birmingham Cancer Research UK Centre (C17422/A25154). The work was funded by the Inflammatory Breast Cancer Network UK. Publisher Copyright: © 2022 S. Karger AG, Basel. Copyright: All rights reserved.
Uncontrolled Keywords: immune cells,inflammatory breast cancer,multiplex immunofluorescence,tumour microenvironment,pathology and forensic medicine,molecular biology,cell biology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2734
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Depositing User: LivePure Connector
Date Deposited: 15 Dec 2022 03:41
Last Modified: 27 Jan 2023 10:30
DOI: 10.1159/000524549

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