Tumor expression of CD200 inhibits IL-10 production by tumor-associated myeloid cells and prevents tumor immune evasion of CTL therapy.
CD200 is a cell-surface glycoprotein that functions through interaction with the CD200 receptor on myeloid lineage cells to regulate myeloid cell functions. Expression of CD200 has been implicated in multiple types of human cancer; however, the impact of tumor expression of CD200 on tumor immunity remains poorly understood. To evaluate this issue, we generated CD200-positive mouse plasmacytoma J558 and mastocytoma P815 cells. We found that established CD200-positive tumors were often completely rejected by adoptively transferred CTL without tumor recurrence; in contrast, CD200-negative tumors were initially rejected by adoptively transferred CTL but the majority of tumors recurred. Tumor expression of CD200 significantly inhibited suppressive activity and IL-10 production by tumor-associated myeloid cells (TAMC), and as a result, more CTL accumulated in the tumor and exhibited a greater capacity to produce IFN-gamma in CD200-positive tumors than in CD200-negative tumors. Neutralization of IL-10 significantly inhibited the suppressor activity of TAMC, and IL-10-deficiency allowed TAMC to kill cancer cells and their antigenic variants, which prevented tumor recurrence during CTL therapy. Thus, tumor expression of CD200 prevents tumor recurrence via inhibiting IL-10 production by TAMC.
Wang
Lixin
L
Department of Pathology and Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, OH 43210, USA.
Liu
Jin-Qing
JQ
Talebian
Fatemeh
F
El-Omrani
Hani Y
HY
Khattabi
Mazin
M
Yu
Li
L
Bai
Xue-Feng
XF
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D020350:Graft vs Tumor Effect / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D034801:Mastocytoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000276:immunology; D009368:Neoplasm Transplantation; D010954:Plasmacytoma / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019076:Transgenes / Q000235:genetics; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; C042739:antigens, CD200