Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden

Abstract

BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.

Dendritic Cell Subpopulations Are Associated with Prognostic Characteristics of Breast Cancer after Neoadjuvant Chemotherapy—An Observational Study

“…In primary invasive BC, we found the highest densities of DC-LAMP + DC in tumors negative for ER and PR [37]. High intra-tumoral DC-LAMP + density was associated with increased odds of multiple lymph node metastases [38]. Additionally, we demonstrated that DC-LAMP + DCs are prevalent in larger tumors with higher nuclear grade and lower expression of ER and PR.…”

“…Our previous studies indicate that density and local composition of various subtypes of DCs (classified by different superficial antigens) is associated with certain morphological and molecular features in a primary and metastatic BC setting, which renders them as prognostic factors, both favorable and unfavorable. Furthermore, the local preponderance alone of distinct DCs subtypes was associated with certain tumor behavior and lower or higher burden of sentinel lymph nodes (SLNs) [36][37][38].…”

Dendritic Cell Subpopulations Are Associated with Morphological Features of Breast Ductal Carcinoma In Situ

“…Cluster of differentiation 123 (CD123) is a marker of plasmacytoid DCs, which are present in the peripheral blood and in inflammatory lymph nodes. The dendritic-cell-lysosome-associated membrane glycoprotein (DC-LAMP3 or CD208) is a marker of mature DCs that appears relatively late during their differentiation [ 8 , 9 ]. DC-LAMP + DCs express multiple ligands to interact with receptors on T cells, possibly being the most active immune regulators of lymphocytes.…”