Sotomayor E M, Borrello I, Rattis F M, Cuenca A G, Abrams J, Staveley-O'Carroll K, Levitsky H I
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Blood. 2001 Aug 15;98(4):1070-7. doi: 10.1182/blood.v98.4.1070.
Tumor antigen-specific T-cell tolerance may limit the efficacy of therapeutic cancer vaccines. Direct presentation of antigens by tumor cells incapable of providing adequate costimulation to tumor-specific T cells has been suggested as the basis for this unresponsiveness. Using parent-into-F1 bone marrow (BM) chimeras, this study unambiguously demonstrates that the induction of this tolerant state requires T-cell recognition of tumor antigen presented by BM-derived antigen-presenting cells (APCs), not tumor cells themselves. In the absence of host APC presentation, tumor-specific T cells remained functional, even in the setting of antigen expressed by B-cell lymphomas residing in secondary lymphoid tissues. The intrinsic APC capacity of tumor cells has therefore little influence over T-cell priming versus tolerance, a decision that is regulated at the level of host APCs. (Blood. 2001;98:1070-1077)
肿瘤抗原特异性T细胞耐受性可能会限制治疗性癌症疫苗的疗效。无法为肿瘤特异性T细胞提供足够共刺激的肿瘤细胞直接呈递抗原，被认为是这种无反应性的基础。本研究利用亲代到F1骨髓（BM）嵌合体，明确证明了这种耐受状态的诱导需要T细胞识别由BM来源的抗原呈递细胞（APC）呈递的肿瘤抗原，而非肿瘤细胞自身。在没有宿主APC呈递的情况下，肿瘤特异性T细胞仍保持功能，即使在二级淋巴组织中存在的B细胞淋巴瘤表达抗原的情况下也是如此。因此，肿瘤细胞的内在APC能力对T细胞启动与耐受的影响很小，这一决定是在宿主APC水平上调节的。（《血液》。2001年；98:1070 - 1077）
