https://orcid.org/0000-0002-2112-4382
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ABSTRACT
Breast cancer is the most common form of cancer in women worldwide. Although the survival among breast cancer patients has improved, there is still a large group of patients with dismal prognosis. One of the most important prognostic factors for poor prognosis is lymph node metastasis. Increasing knowledge concerning the lymph nodes of breast cancer patients indicates that they are affected by the primary tumor. In this study we show that presence of CD169+ subcapsular sinus macrophages in contact with lymph node metastases in breast cancer patients, is related to better prognosis after adjuvant tamoxifen treatment, but only in patients with PDL1+ primary tumors. This is in contrast to the prognostic effect of CD169+ primary tumor-associated macrophages (TAMs). We further show that CD169+ macrophages were spatially associated with expression of PDL1 on nearby cells, both in primary tumors and metastatic lymph node, although PDL1 expression in metastatic lymph node as such did not have further prognostic impact. Our data suggest that CD169+ resident lymph node macrophages have a unique function in targeting immune responses against breast cancer and should be further investigated in detail.
Abbreviations
| APC | = | Antigen presenting cells |
| ER | = | Estrogen receptor |
| HER2 | = | Human epidermal growth factor receptor 2 |
| PDL1 | = | Programmed death-ligand 1 |
| IHC | = | Immunohistochemical |
| MLN | = | Metastatic lymph node |
| PR | = | Progesterone receptor |
| TAM | = | Tumor associated macrophages |
| TMA | = | Tissue microarray |
| PT | = | Primary tumor |
| TNBC | = | Triple negative breast cancer |
Acknowledgments
The authors thank Kristina Lövgren for professional technical skills in preparation of the TMA. The authors thank Kristina Ekström-Holka for professional technical skills in preparation of the IHC. This work was supported by grants from the Swedish Cancer Society; the Swedish Research Council; the Governmental Funding of Clinical Research within the National Health Service (ALF), the UMAS Cancer foundation, the Gunnar Nilsson’s Cancer Foundation, the Åke Wibergs foundation, the Percy Falks Foundation, and the Gyllenstiernska Krapperups foundation.
Author contributions
FBG was responsible for analyzing data and for writing the initial manuscript together with KL. NA and FBG were responsible for annotating the IHC together with KL. LR and MF were responsible for the clinical patient cohort. POB and FBG were responsible for statistical evaluations. KL was responsible for designing the study, for analyzing data and for writing the initial manuscript.
Disclosure of potential conflicts of interest
KL is a board member of Cantargia AB, a company developing IL1RAP inhibitors. This does not alter the Author’s adherence to all guidelines for publication. The authors otherwise declare no competing interest.
Data availability
All datasets generated in the course of the current study are presented in the main text and the Supplementary Information available online.
Supplementary material
Supplemental data for this article can be accessed on the publisher’s website.