Journal article
The immunomodulatory, antitumor and antimetastatic responses of melanoma-bearing normal and alcoholic mice to sunitinib and ALT-803: a combinatorial treatment approach
Cancer immunology, immunotherapy, Vol.65(9), pp.1123-1134
09/2016
Handle:
https://hdl.handle.net/2376/113473
PMID: 27481107
Abstract
ALT-803, a novel IL-15/IL-15 receptor alpha complex, and the tyrosine kinase inhibitor, sunitinib, were examined for their single and combined effects on the growth of subcutaneous B16BL6 melanoma and on lymph node and lung metastasis. The study was conducted in immunocompetent C57BL/6 mice drinking water (Water mice) and in mice that chronically consumed alcohol (Alcohol mice), which are deficient in CD8(+) T cells. Sunitinib inhibited melanoma growth and was more effective in Alcohol mice. ALT-803 did not alter tumor growth or survival in Water or Alcohol mice. Combined ALT-803 and sunitinib inhibited melanoma growth and increased survival, and these effects were greater than sunitinib alone in Water mice. ALT-803 and alcohol independently suppressed lymph node and lung metastasis, whereas sunitinib alone or in combination with ALT-803 increased lymph node and lung metastasis in Water and Alcohol mice. Initially, ALT-803 increased IFN-γ-producing CD8(+)CD44(hi) memory T cells and CD8(+)CD44(hi)CD62L(lo) effector memory T cells and sunitinib decreased immunosuppressive MDSC and T regulatory cells (Treg). However, the impact of these treatments diminished with time. Subcutaneous tumors from Water mice showed increased numbers of CD8(+) T cells, CD8(+)CD44(hi) T cells, NK cells, and MDSC cells and decreased Treg cells after ALT-803 treatment.
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Details
- Title
- The immunomodulatory, antitumor and antimetastatic responses of melanoma-bearing normal and alcoholic mice to sunitinib and ALT-803: a combinatorial treatment approach
- Creators
- Kari A Gaither - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USAAlexander A Little - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USAAlisha A McBride - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USASavanna R Garcia - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USAKiranjot K Brar - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USAZhaohui Zhu - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USAAmity Platt - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USAFaya Zhang - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USAGary G Meadows - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USA. meadows@wsu.eduHui Zhang - Department of Pharmaceutical Sciences and the Pharmaceutical Sciences Graduate Program, College of Pharmacy, Washington State University Spokane, PBS 323, P. O. Box 1495, Spokane, WA, 99210-1495, USA. hzhang@wsu.edu
- Publication Details
- Cancer immunology, immunotherapy, Vol.65(9), pp.1123-1134
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- Germany
- Grant note
- K05 AA017149 / NIAAA NIH HHS R21 AA022098 / NIAAA NIH HHS
- Identifiers
- 99900547767501842
- Language
- English
- Resource Type
- Journal article