Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells.
Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells.
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DOI：
10.1084/jem.20041130
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发表时间：
2004-09-20
期刊：
影响因子：
--
通讯作者：
Houghton AN
中科院分区：
文献类型：
--
作者：
Turk MJ;Guevara-Patiño JA;Rizzuto GA;Engelhorn ME;Sakaguchi S;Houghton AN
伴随的肿瘤免疫描述了在具有在远端部位排斥相同肿瘤的进行性肿瘤的宿主中的免疫应答。在这项工作中，伴随的肿瘤免疫进行了研究，在小鼠携带免疫原性差的B16黑色素瘤。B16肿瘤的进展没有自发地引起伴随免疫。然而，荷瘤小鼠中CD 4 + T细胞的耗竭导致第6天给予的攻击肿瘤的CD 8 + T细胞介导的排斥。伴随免疫也引起了治疗与环磷酰胺或DTA-1单克隆抗体对糖皮质激素诱导的肿瘤坏死因子受体。B16黑色素瘤引起的免疫与一种不同的同基因黑色素瘤交叉反应，但不与非黑色素瘤肿瘤。此外，CD 8 + T细胞从小鼠与伴随的免疫特异性应答的主要组织相容性复合物I类限制性表位的两个黑素细胞分化抗原。用缺乏CD 4 + CD 25+区室的CD 8+和CD 4 + T细胞过继转移的RAG 1 −/−小鼠产生了强烈的伴随免疫，其被再加入CD 4 + CD 25+细胞抑制。天然存在的CD 4 + CD 25 + T细胞有效地抑制由先前活化的CD 8 + T细胞介导的伴随免疫，表明初始宿主中的前体调节性T细胞产生有效的抑制剂。这些结果表明，调节性T细胞是针对这种弱免疫原性肿瘤的伴随肿瘤免疫的主要调节因子。
Concomitant tumor immunity describes immune responses in a host with a progressive tumor that rejects the same tumor at a remote site. In this work, concomitant tumor immunity was investigated in mice bearing poorly immunogenic B16 melanoma. Progression of B16 tumors did not spontaneously elicit concomitant immunity. However, depletion of CD4+ T cells in tumor-bearing mice resulted in CD8+ T cell–mediated rejection of challenge tumors given on day 6. Concomitant immunity was also elicited by treatment with cyclophosphamide or DTA-1 monoclonal antibody against the glucocorticoid-induced tumor necrosis factor receptor. Immunity elicited by B16 melanoma cross-reacted with a distinct syngeneic melanoma, but not with nonmelanoma tumors. Furthermore, CD8+ T cells from mice with concomitant immunity specifically responded to major histocompatibility complex class I–restricted epitopes of two melanocyte differentiation antigens. RAG1 −/− mice adoptively transferred with CD8+ and CD4+ T cells lacking the CD4+CD25+ compartment mounted robust concomitant immunity, which was suppressed by readdition of CD4+CD25+ cells. Naturally occurring CD4+CD25+ T cells efficiently suppressed concomitant immunity mediated by previously activated CD8+ T cells, demonstrating that precursor regulatory T cells in naive hosts give rise to effective suppressors. These results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor.
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影响因子：
5.4
作者：
Ghiringhelli, F;Larmonier, N;Martin, F
通讯作者：
Martin, F
影响因子：
15.3
作者：
DIGIACOMO, A;NORTH, RJ
通讯作者：
NORTH, RJ
影响因子：
6.4
作者：
HOWELL, SB;DEAN, JH;LAW, LW
通讯作者：
LAW, LW
影响因子：
6.4
作者：
BELEHRAD.J;BARSKI, G;THONIER, M
通讯作者：
THONIER, M
DOI：
10.1073/pnas.90.8.3539
发表时间：
1993-04-15
影响因子：
11.1
作者：
DRANOFF, G;JAFFEE, E;MULLIGAN, RC
通讯作者：
MULLIGAN, RC