Joh Joongho, Chilton Paula M, Wilcher Sarah A, Zahin Maryam, Park Jino, Proctor Mary L, Ghim Shin-Je, Jenson Alfred B
James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA; Department of Medicine, University of Louisville, Louisville, KY, USA.
Christine M. Kleinert Institute for Hand & Microsurgery, 225 Abraham Flexner Way, Suite 850, Louisville, KY, USA.
Exp Mol Pathol. 2017 Oct;103(2):181-190. doi: 10.1016/j.yexmp.2017.09.003. Epub 2017 Sep 20.
Previous studies of naturally occurring mouse papillomavirus (PV) MmuPV1-induced tumors in B6.Cg-Foxn1 mice suggest that T cell deficiency is necessary and sufficient for the development of such tumors. To confirm this, MmuPV1-induced tumors were transplanted from T cell-deficient mice into immunocompetent congenic mice. Consequently, the tumors regressed and eventually disappeared. The elimination of MmuPV1-infected skin/tumors in immunocompetent mice was consistent with the induction of antitumor T cell immunity. This was confirmed by adoptive cell experiments using hyperimmune splenocytes collected from graft-recipient mice. In the present study, such splenocytes were injected into T cell-deficient mice infected with MmuPV1, and they eliminated both early-stage and fully formed tumors. We clearly show that anti-tumor T cell immunity activated during tumor regression in immunocompetent mice effectively eliminates tumors developing in T cell-deficient congenic mice. The results corroborate the notion that PV-induced tumors are strongly linked to the immune status of the host, and that PV antigens are major anti-tumor antigens. Successful anti-PV T cell responses should, therefore, lead to effective anti-tumor immune therapy in human PV-infected patients.
先前对B6.Cg-Foxn1小鼠中自然发生的小鼠乳头瘤病毒（PV）MmuPV1诱导的肿瘤的研究表明，T细胞缺陷对于此类肿瘤的发生发展是必要且充分的。为了证实这一点，将MmuPV1诱导的肿瘤从T细胞缺陷小鼠移植到具有免疫活性的同基因小鼠体内。结果，肿瘤消退并最终消失。具有免疫活性的小鼠中MmuPV1感染的皮肤/肿瘤的消除与抗肿瘤T细胞免疫的诱导一致。这通过使用从移植受体小鼠收集的超免疫脾细胞进行的过继细胞实验得到证实。在本研究中，将此类脾细胞注射到感染MmuPV1的T细胞缺陷小鼠中，它们消除了早期和完全形成的肿瘤。我们清楚地表明，在具有免疫活性的小鼠肿瘤消退过程中激活的抗肿瘤T细胞免疫有效地消除了在T细胞缺陷同基因小鼠中发生的肿瘤。这些结果证实了PV诱导的肿瘤与宿主免疫状态密切相关的观点，并且PV抗原是主要的抗肿瘤抗原。因此，成功的抗PV T细胞反应应能在人类PV感染患者中实现有效的抗肿瘤免疫治疗。
