Evaluation of the immunomodulatory activity of thalidomide on tumor-associated macrophages in the 4T1 murine metastatic breast cancer model

D.C Reis,A.C Araújo E Silva,L.C Campos,D.A Gomes,R.C Russo,E Ferreira,P.P Campos,G.D Cassali,S.G.B Pinto,M.A Rodrigues,G.V Moreira,M.T.P Lopes,S.L Fialho

doi:10.1590/1678-4162-12125

Abstract

ABSTRACT The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.

Highlights

The tumor microenvironment comprises different cell types, including stromal and inflammatory cells (Quail and Joyce, 2013)
The 4T1 mouse mammary tumor cell line was obtained from the American Type Culture Collection (Manassas, USA). 4T1 cells were maintained in RPMI 1640 medium (Hyclone, Logan, UT) containing 10% fetal bovine serum (FBS) (Hyclone, Logan, UT), 100 U/ml of penicillin and 100μg/ml of streptomycin (Invitrogen) at 37oC in a humidified atmosphere of 5% CO2
Our findings demonstrated that Thal's prolonged administration exhibited an immunomodulatory and an anti-tumor action in the primary tumor and lung metastases of 4T1 tumor-bearing mice

Summary

Introduction

The tumor microenvironment comprises different cell types, including stromal and inflammatory cells (Quail and Joyce, 2013). Solid tumors are commonly infiltrated with innate immune cells, including tumor-associated macrophages (TAMs), which represent the major inflammatory component of many tumors' stroma (Ruffell et al, 2012; Mei et al, 2016).

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