Li Xiang, Lan Xu, Wang Grace, Liu Yi, Zhao Ke, Lu Shan-Zheng, Xu Xiao-Xi, Shi Gang-Gang, Ye Kui, Zhang Bao-Ren, Zhao Yi-Ming, Han Hong-Qiu, Du Cai-Gan, Ichim Thomas E, Wang Hao
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin General Surgery Institute, Tianjin, China.
Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Transl Oncol. 2018 Aug;11(4):890-899. doi: 10.1016/j.tranon.2018.04.012. Epub 2018 May 21.
The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response.
Full-thickness skin transplantation was performed from C57BL/6 (H-2) donors to BALB/c (H-2) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2 × 10 cells) at the same time. The tumor size and pathological changes, cell populations and cytokine profiles were evaluated at day 14 post-transplantation.
The results showed that as compared to non-transplant group, the allogenic immune response in the skin-grafting group inhibited the growth of tumors, which was significantly associated with increased numbers of intra-tumor infiltrating lymphocytes, increased populations of CD11cMHC-classIICD86 DCs, CD3CD4 T cells, CD3CD8 T cells, and CD19 B cells, as well as decreased percentage of CD4CD25Foxp3 T cells in the spleens. In addition, the levels of serum IgM and IgG, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were significantly higher within the tumor in skin transplant groups than that in non-transplant group.
Allogenic skin transplantation suppresses the tumor growth through activating the allogenic immune response, and it may provide a new immunotherapy option for the clinical refractory tumor treatment.
肿瘤细胞可通过免疫编辑机制逃避免疫清除,这些机制包括产生免疫抑制或免疫调节细胞。相比之下,同种异体移植可激活免疫系统并诱导强烈的同种异体反应。本研究的目的是通过激活同种异体免疫反应来研究同种异体皮肤移植在抑制肿瘤生长方面的疗效。
将C57BL/6(H-2)供体的全层皮肤移植到同时接受皮下注射同基因CT26结肠癌细胞(2×10个细胞)的BALB/c(H-2)受体。在移植后第14天评估肿瘤大小和病理变化、细胞群体和细胞因子谱。
结果显示,与未移植组相比,皮肤移植组的同种异体免疫反应抑制了肿瘤生长,这与肿瘤内浸润淋巴细胞数量增加、CD11cMHC-II类CD86 DC、CD3CD4 T细胞、CD3CD8 T细胞和CD19 B细胞群体增加以及脾脏中CD4CD25Foxp3 T细胞百分比降低显著相关。此外,皮肤移植组肿瘤内血清IgM和IgG、肿瘤坏死因子(TNF)-α和干扰素(IFN)-γ水平明显高于未移植组。
同种异体皮肤移植通过激活同种异体免疫反应抑制肿瘤生长,可能为临床难治性肿瘤治疗提供一种新的免疫治疗选择。