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M2 tumor-associated macrophages play important role in predicting response to neoadjuvant chemotherapy in triple-negative breast carcinoma

  • Preclinical study
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Abstract

Purpose

Two types of macrophages are present in tumor microenvironment. M1 macrophages exhibit potent anti-tumor properties, while M2 macrophages play the pro-tumoral roles. The presence of M2 macrophages is associated with worsened overall survival in triple-negative breast carcinoma (TNBC) patients. However, the relationship between M2 macrophages and response to neoadjuvant chemotherapy (NAC) is unknown.

Methods

M2 macrophages were investigated on biopsy whole sections from 66 TNBCs treated with NAC by CD163 together with other immune checkpoint markers (PD1, PD-L1 and CD8) using a multi-color immunohistochemical multiplex assay.

Results

Incomplete response was significantly associated with older age, lower PD-L1 expression (tumor and stroma), lower levels of CD8-positive TILs in stroma, but higher level of CD163-positive macrophages, with the level of CD163-positive M2 macrophages in peritumoral area as the strongest factor.

Conclusions

Our data have demonstrated that the level of CD163-positive M2 macrophages was significantly higher in TNBC patients with incomplete response than patients with complete response, suggesting M2 macrophages’ important role in predicting TNBC patients’ response to NAC.

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Funding

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Authors and Affiliations

  1. Department of Pathology, Wexner Medical Center, The Ohio State University, 410 W. 10th Ave, Columbus, OH, 43210, USA

    Vidya Arole, Tiansheng Shen, Anil V. Parwani & Zaibo Li

  2. Roche Tissue Diagnostics, Tucson, AZ, 85755, USA

    Hiroaki Nitta

  3. Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University, Columbus, OH, 43210, USA

    Lai Wei

Authors
  1. Vidya Arole
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  2. Hiroaki Nitta
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  3. Lai Wei
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  4. Tiansheng Shen
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  5. Anil V. Parwani
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  6. Zaibo Li
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Contributions

Study design: All. Data collection: VA, TS, HN, AVP, ZL. Data analysis: VA, TS, HN, ZL. Statistical oversight: LW. Manuscript preparation: VA, TS, HN, ZL. Manuscript revision: VA, TS, HN, AVP, ZL. Manuscript approval: All.

Corresponding author

Correspondence to Zaibo Li.

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Conflict of interest

V. Arole, T. Shen, L. Wei, A. Parwani and Z. Li have no financial relationship to disclose. H. Nitta is an employee of Roche Tissue Diagnostics.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Research involving animal rights

This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual patients included in the study.

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Arole, V., Nitta, H., Wei, L. et al. M2 tumor-associated macrophages play important role in predicting response to neoadjuvant chemotherapy in triple-negative breast carcinoma. Breast Cancer Res Treat 188, 37–42 (2021). https://doi.org/10.1007/s10549-021-06260-1

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  • DOI: https://doi.org/10.1007/s10549-021-06260-1

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