Bright Jennifer D, Schultz Heather N, Byrne Jennifer A, Bright Robert K
Department of Immunology and Molecular Microbiology; Texas Tech University Health Sciences Center; Lubbock, TX USA.
Oncoimmunology. 2013 Jul 1;2(7):e25049. doi: 10.4161/onci.25049. Epub 2013 May 21.
Tumor protein D52 (D52) is constitutively expressed in healthy tissues and overexpressed in multiple cancers, including (but not limited to) breast, prostate and ovarian carcinomas. Although the normal functions of D52 are unknown, it is clear that increased D52 expression levels not only stimulate cell proliferation and metastasis, but also correlate with poor prognosis in a subset of breast cancer patients. The murine orthologs of D52 (mD52) shares 86% identity with its human counterpart (hD52) and mirrors hD52 expression patterns. The forced overexpression of mD52 induces anchorage-independent growth in vitro and promotes tumor formation as well as spontaneous metastasis in vivo. We have previously reported that the intramuscular administration of recombinant mD52 elicits immune responses capable of rejecting a challenge with tumor cells and preventing spontaneous metastasis only in 50% of mice. We hypothesized that mechanisms of peripheral tolerance dampen immune responses against mD52, thus limiting the protective effects of vaccination. To test this hypothesis, mice were depleted of CD25 regulatory T cells (Tregs) and subcutaneously immunized with mD52 prior to a tumor challenge. The subcutaneous immunization failed to induce protective antitumor immunity unless accompanied by Treg depletion, which resulted in a rate of protection of 70% as compared with.
肿瘤蛋白D52（D52）在健康组织中组成性表达，在多种癌症中过表达，包括（但不限于）乳腺癌、前列腺癌和卵巢癌。尽管D52的正常功能尚不清楚，但很明显，D52表达水平的升高不仅刺激细胞增殖和转移，而且与一部分乳腺癌患者的预后不良相关。D52的小鼠直系同源物（mD52）与其人类对应物（hD52）具有86%的同一性，并反映hD52的表达模式。mD52的强制过表达在体外诱导不依赖贴壁生长，并促进体内肿瘤形成以及自发转移。我们之前报道，肌肉注射重组mD52仅在50%的小鼠中引发能够排斥肿瘤细胞攻击并预防自发转移的免疫反应。我们假设外周耐受机制会抑制针对mD52的免疫反应，从而限制疫苗接种的保护作用。为了验证这一假设，在肿瘤攻击前，对小鼠进行CD25调节性T细胞（Tregs）清除，并皮下免疫mD52。皮下免疫未能诱导保护性抗肿瘤免疫，除非伴有Treg清除，与……相比，Treg清除后的保护率为70%。
