Thalidomide suppresses melanoma growth by activating natural killer cells in mice.
Although thalidomide (Thd) is being extensively investigated for its effects on cytokine production and T cell costimulation, it is poorly understood whether it is capable of modulating the activities of natural killer (NK) cells. In this study, Thd effects on NK cell activity were examined with a murine model of melanoma, which is mostly rejected by NK cell-dependent mechanism. Administration of Thd significantly (p<0.01 on Day 21) suppressed the growth of subcutaneous B16F1 melanoma. In Thd-treated mice, marked splenomegaly and augmented splenocyte count were observed. Additionally, the percentage of splenic NK1.1+ cells was elevated to approximately 2.5-fold within 10 days after Thd treatment. The expression of interferon inducible protein (IP)-10, interferon (IFN)-gamma, interleukin (IL)-12 and IL-18 was remarkably upregulated. Production of the cytotoxic molecule perforin was also augmented. These data suggest that Thd strongly activates NK cell activity in mice, possibly resulting in enhanced tumor surveillance defense.
Kawamata
Ai
A
Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo 145-8515, Japan. ai@senzoku.showa-u.ac.jp.
Ito
Daisuke
D
Odani
Takeshi
T
Isobe
Tomohide
T
Iwase
Masayasu
M
Hatori
Masashi
M
Nagumo
Masao
M
D000199:Actins / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000187:drug effects; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects*; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013792:Thalidomide / Q000494:pharmacology*
D000199:Actins; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D018664:Interleukin-12; D013792:Thalidomide; D007371:Interferon-gamma; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases