Macrophages polarization and density of tumor-associated dendritic cells correlated with depth of invasion in gastric adenocarcinoma

Edina Lazović Salčin, Svjetlana Radović, Mirsad Dorić, Suada Kuskunović-Vlahovljak, Nina Čamdžić, Mirsad Babić

Abstract


Introduction: Tumor-associated macrophages (TAM) are the most common inflammatory cells in the tumor microenvironment (TM). As a response to microenvironmental signals, they polarize into tumor resisting M1 or promoting M2 macrophages. TAM and tumor-associated dendritic cells (TADC) can either promote tumor growth and tissue invasiveness or have anti-tumor activity. The aim of the study was the examination of prognostic value in the individual cell population in TM and their correlation with clinicopathological parameters of gastric cancer. Materials and Methods: The study analyzed 60 samples of gastric cancer, known status of regional lymph nodes and without dissemination at the time of diagnosis. The control group was normal gastric tissue samples. Traditional parameters of biological aggressiveness, tumor size, histological grade, and lymphovascular invasion, are determined after standard hematoxylin-eosin staining. TAM and TADS have been evaluated using the immunohistochemical method with CD68 (TAM), TNFa (TAM-M1), CD163 (TAM-M2), and S100 (TADC) antibodies. Expression evaluation of the tissue antigen was carried out by semiquantitative methods. Results: There were statistically significant differences of TAM density (P 0.05). Conclusion: TAMs and TADC have shown potential as biomarkers for evaluating the gastric cancer staging and progression. They showed promising prediction in depth of invasion, histological grade of tumor and tumor size. Keywords: gastric cancer, tumor microenvironment, TAM, TAM-M1/M2, TADC

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Pinto-de-Sousa J, David L, Seixas M, Pimenta A. Clinicopathologic profiles and prognosis of gastric carcinoma from the cardia, fundus/body, and antrum. Dig Surg. 2001;18:102–110.

Pantano F, Berti P, Guida FM, Perrone G, Vincenzi B, Amato MMC, et al. The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients. J. Cell. Mol. Med. 2013;Vol17(11):1415-1421.

Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? The LANCET. 2001;357: 539–45.

Peng J, Ding T, Zheng LM, Shao JY. Influence of tumor-associated macrophages on progression and prognosis of nasopharyngeal carcinoma. Ai Zheng. 2006;25:1340–1345.

Forssell J, Oberg A, Henriksson ML, Stenling R, Jung A, Palmqvist R. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res. 2007;13:1472–1479.

Ohri CM, Shikotra A, Green RH, Waller DA, Bradding P. Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival. Eur Respir J. 2009;33:118–126.

Qiang Zhou, Rui-Qing Peng, Xiao-Jun Wu, Qing Xia, Jing-Hui Hou, Ya Ding, et al. The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer. J Transl Med. 2010;8:13.

Guo SJ, Lin DM, Li J, Liu RZ, Zhou CX, Wang DM, et al. Tumor-associated macrophages and CD3-zeta expression of tumor-infiltrating lymphocytes in human esophageal squamous-cell carcinoma. Dis Esophagus. 2007;20:107–116.

Cardoso AP, Pinto ML, Pinto AT, Oliveira MI, Pinto MT, Gonçalves R et al. Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y1086, c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity. Oncogene. 2014;33(16):2123-33.

Saito H, Tsujitani S, Ikeguchi M, Maeta M, Kaibara N. Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer. 1998;78:1573-1577.

Zheng Y, Cai Z, Wang S, Zhang X, Qian J, Hong S, et al. Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis. Blood. 2009;114:3625–8.

Ohno S, Inagawa H, Dhar DK, Fujii T, Ueda S, Tachibana M, et al. The Degree of Macrophage Infiltration into the Cancer Cell Nest is a Significant Predictor of Survival in Gastric Cancer Patients. Anticancer Research. 2003;23: 5015-5022.

Hilly O, Koren R, Raz R, Rath-Wolfson L, Mizrachi A, Hamzany Y, et al. The Role of S100-Positive Dendritic Cells in the Prognosis of Papillary Thyroid Carcinoma. American Journal of Clinical Pathology. 2013;139:87-92.

Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, et al. CD8+ T Cells Infiltrated within Cancer Cell Nests as a Prognostic Factor in Human Colorectal Cancer. Cancer Research. 1998;58:3491-3494.

Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002;196:254–265.;

Song L, Asgharzadeh S, Salo J, Engell K, Wu HW, Sposto R, et al. Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. J Clin Invest. 2009;119:1524–36.

Jensen TO, Schmidt H, Moller HJ, Hoyer M, Maniecki MB, Sjoegren P, et al. Macrophage markers in serum and tumor have prognostic impact in American Joint Committee on Cancer stage I/II melanoma. J Clin Oncol. 2009;27:3330–7.

Kurahara H, Shinchi H, Mataki Y, Maemura K, Noma H, Kubo F, et al. Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res. 2011;167:211–9.

Welsh TJ, Green RH, Richardson D, Waller DA, O'Byrne KJ, Bradding P. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol. 2005;23:8959–67.

Shi-Yun Tan, Yan Fan, He-Sheng Luo, Zhi-Xiang Shen, Yi Guo, Liang-Jia Zhao. Prognostic significance of cell infiltrations of immunosurveillance in colorectal cancer. World J Gastroenterol. 2005;11:1210–1214.

Ma J, Liu L, Che G, Yu N, Dai F, You Z. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer. 2010;10:112.

Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Okumura H, Matsumoto M, et al. Tumor-associated macrophage (TAM) infiltration in gastric cancer. Anticancer Res. 2003;23(5A):4079–83.

Ohno S, Inagawa H, Dhar DK, Fujii T, Ueda S, Tachibana M, et al. Role of tumor-associated macrophages (TAM) in advanced gastric carcinoma: the impact on FasL-mediated counterattack. Anticancer Res. 2005;25:463–70.

Crumley AB, Going JJ, Hilmy M, Dutta S, Tannahill C, McKernan M, et al. Interrelationships between Tumor Proliferative Activity, Leucocyte and Macrophage Infiltration, Systemic Inflammatory Response, and Survival in Patients Selected for Potentially Curative Resection for Gastroesophageal Cancer. Ann Surg Oncol. 2011; 18(9):2604-12.

Osinsky S, Bubnovskaya L, Ganusevich I, Kovelskaya A, Gumenyuk L, Olijnichenko G, et al. Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival. Clin Transl Oncol. 2011;13(2):133–8.

Ma YY, He XJ, Wang HJ, Xia YJ, Wang SL, Ye ZY, et al. Interaction of coagulation factors and tumor associated macrophages mediates migration and invasion of gastric cancer. Cancer Science. 2011;102:336–342.

Wu MS, Lee WJ, Hua KT, Kuo ML, Lin MT. Macrophage Infiltration Induces Gastric Cancer Invasiveness by Activating the β-Catenin Pathway. Research article. PLoS One 2015;10(7).

Yamaguchi T, Fushida S, Yamamoto Y, Tsukada T, Kinoshita J, Oyama K, et al. Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination. Gastric Cancer. 2016;19(4):1052-1065.

Zhang J, Yan Y, Yang Y, Wang L, Li M, Wang J, et al. High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates With the Phenomenon of EMT. Medicine. 2016;95(6).

Tsujitani S, Kakeji Y,Watanabe A, Kohnoe S, Maehara Y, Sugimachi, et al. Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer. Cancer. 1993;66(9):2012-2016.

Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, et al. Macrophage polarization in tumour progression. Semin Cancer Biol. 2008;18(5):349-55.


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