The tumor immunosuppressive microenvironment impairs the therapy of anti-HER2/neu antibody.
10.1007/s13238-012-2044-3
- Author:
Meng XU
1
;
Xuexiang DU
;
Mingyue LIU
;
Sirui LI
;
Xiaozhu LI
;
Yang-Xin FU
;
Shengdian WANG
Author Information
1. Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antibodies, Monoclonal;
immunology;
therapeutic use;
Breast Neoplasms;
drug therapy;
immunology;
pathology;
Cell Line, Tumor;
Female;
Humans;
Immune Tolerance;
immunology;
Mice;
Mice, Inbred BALB C;
Neoplasm Transplantation;
Receptor, ErbB-2;
immunology;
Tumor Microenvironment;
immunology
- From:
Protein & Cell
2012;3(6):441-449
- CountryChina
- Language:English
-
Abstract:
It has been well established that immune surveillance plays critical roles in preventing the occurrence and progression of tumor. More and more evidence in recent years showed the host anti-tumor immune responses also play important roles in the chemotherapy and radiotherapy of cancers. Our previous study found that tumor- targeting therapy of anti-HER2/neu mAb is mediated by CD8(+) T cell responses. However, we found here that enhancement of CD8(+) T cell responses by combination therapy with IL-15R/IL-15 fusion protein or anti-CD40, which are strong stimultors for T cell responses, failed to promote the tumor therapeutic effects of anti-HER2/neu mAb. Analysis of tumor microenviornment showed that tumor tissues were heavily infiltrated with the immunosuppressive macrophages and most tumor infiltrating T cells, especially CD8(+) T cells, expressed high level of inhibitory co-signaling receptor PD-1. These data suggest that tumor microenvironment is dominated by the immunosuppressive strategies, which thwart anti-tumor immune responses. Therefore, the successful tumor therapy should be the removal of inhibitory signals in the tumor microenvironment in combination with other therapeutic strategies.
