Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes
Background: It is increasingly recognized that cancer progression induces systemic immune changes in the host. Alterations in number and function of immune cells have been identified in cancer patients’ peripheral blood and lymphoid organs. Recently, we found dysregulated cytokine signaling in perip...
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doaj-6247d0c39cf241688e34d8d5634906cc2020-11-25T00:30:54ZengElsevierEBioMedicine2352-39642020-02-0152Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytesLei Wang0Diana L. Simons1Xuyang Lu2Travis Y. Tu3Christian Avalos4Andrew Y. Chang5Frederick M. Dirbas6John H. Yim7James Waisman8Peter P. Lee9Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USADepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USADepartment of Biostatistics, UCLA, Los Angeles, CA 90095, USADepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USADepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USADepartment of Medicine, Stanford University Medical Center, Stanford, CA 94305, USADepartment of Surgery, Stanford University, Stanford, CA 94305, USADepartment of Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USADepartment of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USADepartment of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA; Corresponding author.Background: It is increasingly recognized that cancer progression induces systemic immune changes in the host. Alterations in number and function of immune cells have been identified in cancer patients’ peripheral blood and lymphoid organs. Recently, we found dysregulated cytokine signaling in peripheral blood T cells from breast cancer (BC) patients, even those with localized disease. Methods: We used phosphoflow cytometry to determine the clinical significance of cytokine signaling responsiveness in peripheral blood monocytes from non-metastatic BC patients at diagnosis. We also examined the correlation between cytokine signaling in peripheral monocytes and the number of tumor-infiltrating macrophages in paired breast tumors. Findings: Our results show that cytokine (IFNγ) signaling may also be dysregulated in peripheral blood monocytes at diagnosis, specifically in BC patients who later relapsed. Some patients exhibited concurrent cytokine signaling defects in monocytes and lymphocytes at diagnosis, which predict the risk of future relapse in two independent cohorts of BC patients. Moreover, IFNγ signaling negatively correlates with expression of CSF1R on monocytes, thus modulating their ability to infiltrate into tumors. Interpretation: Our results demonstrate that tumor-induced systemic immune changes are evident in peripheral blood immune cells for both myeloid and lymphoid lineages, and point to cytokine signaling responsiveness as important biomarkers to evaluate the overall immune status of BC patients. Funding: This study was supported by the Department of Defense Breast Cancer Research Program (BCRP), The V Foundation, Stand Up to Cancer (SU2C), and Breast Cancer Research Foundation (BCRF). Keywords: Breast cancer, Systemic immunity, Cytokine, Signal transduction, Peripheral monocytes, Peripheral lymphocytes, Clinical outcomehttp://www.sciencedirect.com/science/article/pii/S2352396420300062 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lei Wang Diana L. Simons Xuyang Lu Travis Y. Tu Christian Avalos Andrew Y. Chang Frederick M. Dirbas John H. Yim James Waisman Peter P. Lee |
spellingShingle |
Lei Wang Diana L. Simons Xuyang Lu Travis Y. Tu Christian Avalos Andrew Y. Chang Frederick M. Dirbas John H. Yim James Waisman Peter P. Lee Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes EBioMedicine |
author_facet |
Lei Wang Diana L. Simons Xuyang Lu Travis Y. Tu Christian Avalos Andrew Y. Chang Frederick M. Dirbas John H. Yim James Waisman Peter P. Lee |
author_sort |
Lei Wang |
title |
Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes |
title_short |
Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes |
title_full |
Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes |
title_fullStr |
Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes |
title_full_unstemmed |
Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes |
title_sort |
breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2020-02-01 |
description |
Background: It is increasingly recognized that cancer progression induces systemic immune changes in the host. Alterations in number and function of immune cells have been identified in cancer patients’ peripheral blood and lymphoid organs. Recently, we found dysregulated cytokine signaling in peripheral blood T cells from breast cancer (BC) patients, even those with localized disease. Methods: We used phosphoflow cytometry to determine the clinical significance of cytokine signaling responsiveness in peripheral blood monocytes from non-metastatic BC patients at diagnosis. We also examined the correlation between cytokine signaling in peripheral monocytes and the number of tumor-infiltrating macrophages in paired breast tumors. Findings: Our results show that cytokine (IFNγ) signaling may also be dysregulated in peripheral blood monocytes at diagnosis, specifically in BC patients who later relapsed. Some patients exhibited concurrent cytokine signaling defects in monocytes and lymphocytes at diagnosis, which predict the risk of future relapse in two independent cohorts of BC patients. Moreover, IFNγ signaling negatively correlates with expression of CSF1R on monocytes, thus modulating their ability to infiltrate into tumors. Interpretation: Our results demonstrate that tumor-induced systemic immune changes are evident in peripheral blood immune cells for both myeloid and lymphoid lineages, and point to cytokine signaling responsiveness as important biomarkers to evaluate the overall immune status of BC patients. Funding: This study was supported by the Department of Defense Breast Cancer Research Program (BCRP), The V Foundation, Stand Up to Cancer (SU2C), and Breast Cancer Research Foundation (BCRF). Keywords: Breast cancer, Systemic immunity, Cytokine, Signal transduction, Peripheral monocytes, Peripheral lymphocytes, Clinical outcome |
url |
http://www.sciencedirect.com/science/article/pii/S2352396420300062 |
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