TY - JOUR
T1 - Landscapes of cellular phenotypic diversity in breast cancer xenografts and their impact on drug response
AU - IMAXT Consortium
AU - Georgopoulou, Dimitra
AU - Callari, Maurizio
AU - Rueda, Oscar M.
AU - Shea, Abigail
AU - Martin, Alistair
AU - Giovannetti, Agnese
AU - Qosaj, Fatime
AU - Dariush, Ali
AU - Chin, Suet Feung
AU - Carnevalli, Larissa S.
AU - Provenzano, Elena
AU - Greenwood, Wendy
AU - Lerda, Giulia
AU - Esmaeilishirazifard, Elham
AU - O’Reilly, Martin
AU - Serra, Violeta
AU - Bressan, Dario
AU - Ali, H. R.
AU - Al Sa’d, M.
AU - Alon, S.
AU - Aparicio, S.
AU - Battistoni, G.
AU - Balasubramanian, S.
AU - Becker, R.
AU - Bodenmiller, B.
AU - Boyden, E. S.
AU - Bressan, D.
AU - Bruna, A.
AU - Burger, Marcel
AU - Caldas, C.
AU - Callari, M.
AU - Cannell, I. G.
AU - Casbolt, H.
AU - Chornay, N.
AU - Cui, Y.
AU - Dariush, A.
AU - Dinh, K.
AU - Emenari, A.
AU - Eyal-Lubling, Y.
AU - Fan, J.
AU - Fatemi, A.
AU - Fisher, E.
AU - González-Solares, E. A.
AU - González-Fernández, C.
AU - Goodwin, D.
AU - Greenwood, W.
AU - Grimaldi, F.
AU - Hannon, G. J.
AU - Harris, O.
AU - Mills, Gordon B.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.
AB - The heterogeneity of breast cancer plays a major role in drug response and resistance and has been extensively characterized at the genomic level. Here, a single-cell breast cancer mass cytometry (BCMC) panel is optimized to identify cell phenotypes and their oncogenic signalling states in a biobank of patient-derived tumour xenograft (PDTX) models representing the diversity of human breast cancer. The BCMC panel identifies 13 cellular phenotypes (11 human and 2 murine), associated with both breast cancer subtypes and specific genomic features. Pre-treatment cellular phenotypic composition is a determinant of response to anticancer therapies. Single-cell profiling also reveals drug-induced cellular phenotypic dynamics, unravelling previously unnoticed intra-tumour response diversity. The comprehensive view of the landscapes of cellular phenotypic heterogeneity in PDTXs uncovered by the BCMC panel, which is mirrored in primary human tumours, has profound implications for understanding and predicting therapy response and resistance.
UR - http://www.scopus.com/inward/record.url?scp=85103744076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103744076&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-22303-z
DO - 10.1038/s41467-021-22303-z
M3 - Article
C2 - 33790302
AN - SCOPUS:85103744076
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1998
ER -