title: l-arginine and docetaxel synergistically enhance anti-tumor immunity by modifying the immune status of tumor-bearing mice.
abstract: l-arginine (l-Arg) supplementation has been reported to enhance the function of immune cells, including dendritic cells (DCs) and T lymphocytes, in cancer models thereby countering the suppressive effects of myeloid-derived suppressor cells (MDSCs). The balance of the active immune cells is one factor that determines the progression of cancers in vivo. Docetaxel (DTX), an immunomodulatory chemotherapeutic agent, is now widely used in several types of malignancies including breast cancer. We hypothesized that the combination of DTX and l-Arg would elicit a more robust antitumor response than either molecule alone. To test this hypothesis we utilized BALB/c mice inoculated with 4T1 mammary carcinoma cells. DTX and l-Arg synergistically limited tumor growth in vivo and moderately increased the life span of tumor bearing mice. The anti-tumor effects were associated with the proliferation of splenic CD8(+) CTL and CD4(+) Th1 effector cells, as well as increased serum levels of interferon gamma. More importantly, DTX+l-Arg effectively increased anti-tumor immunity within the tumor microenvironment. Furthermore, the combined therapy increased the number of myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, potent activators of the T cell response, and enhanced expression of the maturation markers CD86 and MHC II (required for antigen presentation). The combination therapy also reduced the proliferation of MDSCs. These data suggest that DTX+l-Arg may be a novel therapeutic strategy for breast cancer patients.
authors.affiliation: Department of Surgical Oncology and Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Yunting
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Medical Examination Center, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Surgical Oncology and Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China. Electronic address: jinfeng66cn@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001120:Arginine / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D000077143:Docetaxel; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects* / Q000502:physiology; D043823:Taxoids / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D001120:Arginine
keywords: Anti-tumor immunity; Breast cancer; Docetaxel; l-arginine