Multiplexed immunofluorescence identifies high stromal CD68+PD-L1+ macrophages as a predictor of improved survival in triple negative breast cancer.

Wang, J; Browne, L; Slapetova, I; Shang, F; Lee, K; Lynch, J; Beretov, J; Whan, R; Graham, PH; Millar, EKA

Multiplexed immunofluorescence identifies high stromal CD68+PD-L1+ macrophages as a predictor of improved survival in triple negative breast cancer.

Wang, J Browne, L Slapetova, I Shang, F Lee, K Lynch, J Beretov, J Whan, R Graham, PH Millar, EKA

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Publisher:: Springer Science and Business Media LLC
Publication Type:: Journal Article
Citation:: Sci Rep, 2021, 11, (1), pp. 21608
Issue Date:: 2021-11-03

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Field	Value	Language
dc.contributor.author	Wang, J
dc.contributor.author	Browne, L
dc.contributor.author	Slapetova, I
dc.contributor.author	Shang, F
dc.contributor.author	Lee, K
dc.contributor.author	Lynch, J
dc.contributor.author	Beretov, J
dc.contributor.author	Whan, R
dc.contributor.author	Graham, PH
dc.contributor.author	Millar, EKA
dc.date.accessioned	2022-05-16T06:57:40Z
dc.date.available	2021-10-15
dc.date.available	2022-05-16T06:57:40Z
dc.date.issued	2021-11-03
dc.identifier.citation	Sci Rep, 2021, 11, (1), pp. 21608
dc.identifier.issn	2045-2322
dc.identifier.issn	2045-2322
dc.identifier.uri	http://hdl.handle.net/10453/157426
dc.description.abstract	Triple negative breast cancer (TNBC) comprises 10-15% of all breast cancers and has a poor prognosis with a high risk of recurrence within 5 years. PD-L1 is an important biomarker for patient selection for immunotherapy but its cellular expression and co-localization within the tumour immune microenvironment and associated prognostic value is not well defined. We aimed to characterise the phenotypes of immune cells expressing PD-L1 and determine their association with overall survival (OS) and breast cancer-specific survival (BCSS). Using tissue microarrays from a retrospective cohort of TNBC patients from St George Hospital, Sydney (n = 244), multiplexed immunofluorescence (mIF) was used to assess staining for CD3, CD8, CD20, CD68, PD-1, PD-L1, FOXP3 and pan-cytokeratin on the Vectra Polaris™ platform and analysed using QuPath. Cox multivariate analyses showed high CD68+PD-L1+ stromal cell counts were associated with improved prognosis for OS (HR 0.56, 95% CI 0.33-0.95, p = 0.030) and BCSS (HR 0.47, 95% CI 0.25-0.88, p = 0.018) in the whole cohort and in patients receiving chemotherapy, improving incrementally upon the predictive value of PD-L1+ alone for BCSS. These data suggest that CD68+PD-L1+ status can provide clinically useful prognostic information to identify sub-groups of patients with good or poor prognosis and guide treatment decisions in TNBC.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartof	Sci Rep
dc.relation.isbasedon	10.1038/s41598-021-01116-6
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Antigens, CD
dc.subject.mesh	Antigens, Differentiation, Myelomonocytic
dc.subject.mesh	Antineoplastic Combined Chemotherapy Protocols
dc.subject.mesh	B7-H1 Antigen
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	Female
dc.subject.mesh	Fluorescent Antibody Technique
dc.subject.mesh	Follow-Up Studies
dc.subject.mesh	Humans
dc.subject.mesh	Lymphocytes, Tumor-Infiltrating
dc.subject.mesh	Macrophages
dc.subject.mesh	Middle Aged
dc.subject.mesh	Prognosis
dc.subject.mesh	Retrospective Studies
dc.subject.mesh	Stromal Cells
dc.subject.mesh	Survival Rate
dc.subject.mesh	Triple Negative Breast Neoplasms
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Lymphocytes, Tumor-Infiltrating
dc.subject.mesh	Macrophages
dc.subject.mesh	Stromal Cells
dc.subject.mesh	Humans
dc.subject.mesh	Antineoplastic Combined Chemotherapy Protocols
dc.subject.mesh	Antigens, CD
dc.subject.mesh	Antigens, Differentiation, Myelomonocytic
dc.subject.mesh	Fluorescent Antibody Technique
dc.subject.mesh	Prognosis
dc.subject.mesh	Survival Rate
dc.subject.mesh	Retrospective Studies
dc.subject.mesh	Follow-Up Studies
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Triple Negative Breast Neoplasms
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	B7-H1 Antigen
dc.title	Multiplexed immunofluorescence identifies high stromal CD68+PD-L1+ macrophages as a predictor of improved survival in triple negative breast cancer.
dc.type	Journal Article
utslib.citation.volume	11
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2022-05-16T06:57:35Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	11
utslib.citation.issue	1

Abstract:

Triple negative breast cancer (TNBC) comprises 10-15% of all breast cancers and has a poor prognosis with a high risk of recurrence within 5 years. PD-L1 is an important biomarker for patient selection for immunotherapy but its cellular expression and co-localization within the tumour immune microenvironment and associated prognostic value is not well defined. We aimed to characterise the phenotypes of immune cells expressing PD-L1 and determine their association with overall survival (OS) and breast cancer-specific survival (BCSS). Using tissue microarrays from a retrospective cohort of TNBC patients from St George Hospital, Sydney (n = 244), multiplexed immunofluorescence (mIF) was used to assess staining for CD3, CD8, CD20, CD68, PD-1, PD-L1, FOXP3 and pan-cytokeratin on the Vectra Polaris™ platform and analysed using QuPath. Cox multivariate analyses showed high CD68+PD-L1+ stromal cell counts were associated with improved prognosis for OS (HR 0.56, 95% CI 0.33-0.95, p = 0.030) and BCSS (HR 0.47, 95% CI 0.25-0.88, p = 0.018) in the whole cohort and in patients receiving chemotherapy, improving incrementally upon the predictive value of PD-L1+ alone for BCSS. These data suggest that CD68+PD-L1+ status can provide clinically useful prognostic information to identify sub-groups of patients with good or poor prognosis and guide treatment decisions in TNBC.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/157426