TY - JOUR
T1 - Characterization of the immune microenvironment in inflammatory breast cancer using multiplex immunofluorescence
AU - Badr, Nahla M.
AU - McMurray, Jack L.
AU - Danial, Irini
AU - Hayward, Steven
AU - Asaad, Nancy Y.
AU - Abd El-Wahed, Moshira M.
AU - Abdou, Asmaa G.
AU - Serag El-Dien, Marwa M.
AU - Sharma, Nisha
AU - Horimoto, Yoshiya
AU - Sircar, Tapan
AU - Vidya, Raghavan
AU - Hoar, Fiona
AU - Rea, Daniel
AU - Jones, J. Louise
AU - Stevens, Andrea
AU - Spooner, David
AU - Merard, Reena
AU - Lewis, Paul
AU - Hunter, Kelly John
AU - Berditchevski, Fedor
AU - Shaaban, Abeer M.
N1 - 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.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Immune cells
KW - Inflammatory breast cancer
KW - Multiplex immunofluorescence
KW - Tumour microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85133141933&partnerID=8YFLogxK
U2 - 10.1159/000524549
DO - 10.1159/000524549
M3 - Article
C2 - 35705026
AN - SCOPUS:85133141933
VL - 90
SP - 31
EP - 43
JO - Pathobiology
JF - Pathobiology
SN - 1015-2008
IS - 1
ER -
