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

James Wang; Lois Browne; Iveta Slapetova; Fei Shang; Kirsty Lee; Jodi Lynch; Julia Beretov; Renee Whan; Peter H. Graham; Ewan K. A. Millar

doi:10.1038/s41598-021-01116-6

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

James Wang, Lois Browne, Iveta Slapetova, Fei Shang, Kirsty Lee, Jodi Lynch, Julia Beretov, Renee Whan, Peter H. Graham, Ewan K. A. Millar

Western Sydney University

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32 Citations (Scopus)

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.

Original language	English
Article number	21608
Number of pages	12
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-01116-6
Publication status	Published - Dec 2021

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© 2021, The Author(s).

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title = "Multiplexed immunofluorescence identifies high stromal CD68+PD{"}{\textquoteleft}L1+ macrophages as a predictor of improved survival in triple negative breast cancer",

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{\texttrademark} 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.",

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AU - Wang, James

AU - Browne, Lois

AU - Slapetova, Iveta

AU - Shang, Fei

AU - Lee, Kirsty

AU - Lynch, Jodi

AU - Beretov, Julia

AU - Whan, Renee

AU - Graham, Peter H.

AU - Millar, Ewan K. A.

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AB - 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.

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

Abstract

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