title: Tumor-associated macrophages in human breast cancer parenchyma negatively correlate with lymphatic metastasis after neoadjuvant chemotherapy.
abstract: Breast cancer is the leading cause of cancer death in women worldwide with high morbidity and mortality. Tumor-associated macrophages (TAM) are major innate immune cells in the tumor microenvironment controlling primary tumor growth and metastasis. Neoadjuvant chemotherapy (NACT) is a conventional pre-operative treatment for breast cancer. In the present study we examined the distribution of TAM in five distinct intratumoral morphological compartments of human breast cancer and their correlation with clinical parameters after NACT. Our data indicated that CD68+ but not stabilin-1+ TAM in areas with parenchymal elements negatively correlate with lymphatic metastasis after NACT. However, in cases where lymphatic metastases were detected (28 out of 50 analyzed samples) both amount of CD68+ and stabilin-1+ macrophages in the areas with coarse fibrous stroma directly correlated with the number of positive lymph nodes. In patients with complete response to the preoperative NACT the average score of CD68 expression in the areas with coarse fibrous stroma was lower compared with cases of a partial response and stable disease. We concluded that function of TAM after NACT depends on their intratumoral localization and local tumor microenvironment which plays an important role in polarization of macrophages towards tumor-suppressive or tumor-supportive types.
authors: Laboratory of Translational Cellular and Molecular Biomedicine, Tomsk State University, Pr. Lenina, 36, 634050 Tomsk, Russia; Siberian State Medical University, Moskovskiy Trakt, 2, 634050 Tomsk, Russia; Tomsk Cancer Research Institute, Per. Kooperativny, 5, 634050 Tomsk, Russia.
authors: Irina
authors: I
authors: Mitrofanova
authors: Laboratory of Translational Cellular and Molecular Biomedicine, Tomsk State University, Pr. Lenina, 36, 634050 Tomsk, Russia; Siberian State Medical University, Moskovskiy Trakt, 2, 634050 Tomsk, Russia.
authors: Marina
authors: M
authors: Zavyalova
authors: Siberian State Medical University, Moskovskiy Trakt, 2, 634050 Tomsk, Russia.
authors: Nadezhda
authors: N
authors: Telegina
authors: Laboratory of Translational Cellular and Molecular Biomedicine, Tomsk State University, Pr. Lenina, 36, 634050 Tomsk, Russia; Tomsk Cancer Research Institute, Per. Kooperativny, 5, 634050 Tomsk, Russia.
authors: Mikhail
authors: M
authors: Buldakov
authors: Laboratory of Translational Cellular and Molecular Biomedicine, Tomsk State University, Pr. Lenina, 36, 634050 Tomsk, Russia; Department of Innate Immunity and Tolerance, Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors: Vladimir
authors: V
authors: Riabov
authors: Laboratory of Translational Cellular and Molecular Biomedicine, Tomsk State University, Pr. Lenina, 36, 634050 Tomsk, Russia; Tomsk Cancer Research Institute, Per. Kooperativny, 5, 634050 Tomsk, Russia.
authors: Nadezhda
authors: N
authors: Cherdyntseva
authors: Laboratory of Translational Cellular and Molecular Biomedicine, Tomsk State University, Pr. Lenina, 36, 634050 Tomsk, Russia; Department of Innate Immunity and Tolerance, Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; German Red Cross Blood Service Baden-Württemberg - Hessen, Friedrich-Ebert Str. 107, 68167 Mannheim, Germany. Electronic address: julia.kzhyshkowska@medma.uni-heidelberg.de.
authors: Julia
authors: J
authors: Kzhyshkowska
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000276:immunology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015816:Cell Adhesion Molecules, Neuronal; D016201:Receptors, Lymphocyte Homing; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C449926:STAB1 protein, human
keywords: Breast cancer; CD68; Intratumoral heterogeneity; Lymphatic metastasis; Neoadjuvant chemotherapy; Stabilin-1; Tumor-associated macrophages