Kottke Timothy, Sanchez-Perez Luis, Diaz Rosa Maria, Thompson Jill, Chong Heung, Harrington Kevin, Calderwood Stuart K, Pulido Jose, Georgopoulos Nick, Selby Peter, Melcher Alan, Vile Richard
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55902, USA.
Cancer Res. 2007 Dec 15;67(24):11970-9. doi: 10.1158/0008-5472.CAN-07-2259.
A close connectivity between autoimmune and tumor rejection responses is known to exist in the case of melanoma immunotherapy. However, relatively little is known about self-antigens on other types of normal cells, their relation to the development of autoimmune disease, and their possible coexistence as potential tumor rejection antigens on associated tumors. In the current study, we induced inflammatory killing of normal prostate tissue in situ using a fusogenic membrane glycoprotein along with the immune adjuvant hsp70. We show here that, in the prostate, hsp70 induces interleukin (IL)-6, which triggers a CD4- and CD8-dependent progressive autoimmune reactivity, associated with IL-17 expression. This autoimmune response was also able to induce the rejection of established prostate tumors, but not other histologic types of tumors, growing elsewhere in the animal. These data show that the intimate connectivity between autoimmune and tumor rejection responses extends beyond the classic melanoma paradigm and may be clinically valuable for the treatment of established metastatic disease of the prostate.
已知在黑色素瘤免疫治疗中，自身免疫反应与肿瘤排斥反应之间存在紧密的联系。然而，对于其他类型正常细胞上的自身抗原、它们与自身免疫性疾病发展的关系，以及它们作为相关肿瘤上潜在的肿瘤排斥抗原可能的共存情况，我们了解得相对较少。在当前的研究中，我们使用一种融合膜糖蛋白以及免疫佐剂hsp70原位诱导正常前列腺组织的炎性杀伤。我们在此表明，在前列腺中，hsp70诱导白细胞介素（IL）-6，其触发依赖于CD4和CD8的进行性自身免疫反应性，与IL-17表达相关。这种自身免疫反应也能够诱导已建立的前列腺肿瘤的排斥，但不能诱导在动物其他部位生长的其他组织学类型肿瘤的排斥。这些数据表明，自身免疫反应与肿瘤排斥反应之间的紧密联系超出了经典的黑色素瘤模式，可能对治疗已确诊的前列腺转移性疾病具有临床价值。
