Early-appearing tumour-infiltrating natural killer cells play a crucial role in the generation of anti-tumour T lymphocytes.
Early-appearing tumour-infiltrating natural killer cells play a crucial role in the generation of anti-tumour T lymphocytes.
复制标题
早期出现的肿瘤浸润自然杀伤细胞在抗肿瘤 T 淋巴细胞的生成中发挥着至关重要的作用。
作者：
Shin Kurosawa;M. Harada;G. Matsuzaki;Y. Shinomiya;H. Terao;N. Kobayashi;K. Nomoto
在肿瘤发生的早期，自然杀伤(NK)细胞渗入原发肿瘤部位，检测它们是否参与抗肿瘤细胞毒性T淋巴细胞(CTL)的产生。用抗NK1.1单抗(MAb)检测到的NK细胞在腹腔注射后第3天和第7天腹膜渗出液细胞(PEC)中的NK细胞明显增加。同基因B16黑色素瘤细胞的接种。这些肿瘤浸润性NK细胞对NK敏感的YAC-1细胞表现出高水平的细胞毒活性，并增加了干扰素-γ和白介素2(IL-2)的表达。用抗NK1.1单抗体内耗竭NK细胞。接种B16黑色素瘤细胞，与NK细胞未耗尽的小鼠相比，PEC中的肿瘤细胞数量增加。有趣的是，两组在第7天和第14天的肿瘤细胞数量的差异比第3天更明显，这强烈地表明早期浸润性NK细胞对随后的抗肿瘤反应有很大的影响。在用黑色素瘤细胞免疫之前，体内NK细胞的耗尽破坏了体外重新刺激后脾细胞产生CD8+肿瘤特异性CTL的能力。这种产生抗肿瘤CTL的能力可以通过额外的ip部分恢复。在黑色素瘤细胞免疫的同时注射重组IL-2和/或干扰素-γ。在与黑色素瘤细胞体外再刺激之前，NK细胞的体外耗尽部分地损害了免疫小鼠脾细胞产生的抗肿瘤CTL。最后，在用黑色素瘤细胞免疫之前，体内NK细胞的耗尽取消了对黑色素瘤细胞的保护性免疫。总之，这些结果表明，早期出现的肿瘤浸润性NK细胞不仅参与了自身的抗肿瘤早期防御，而且在抗肿瘤CTL的产生中起着至关重要的作用。
Natural killer (NK) cells that infiltrated into the primary tumour site at an early stage of tumour development, were examined for their participation in the generation of anti-tumour cytotoxic T lymphocytes (CTL). NK cells, which were detected by anti-NK1.1 monoclonal antibody (mAb), increased in the peritoneal exudate cells (PEC) on days 3 and 7 after an intraperitoneal (i.p.) inoculation of syngeneic B16 melanoma cells. These tumour-infiltrating NK cells showed a high level of cytotoxic activity against NK-sensitive YAC-1 cells and an increased expression of interferon-gamma (IFN-gamma) mRNA and interleukin-2 (IL-2) mRNA. The in vivo depletion of NK cells with anti-NK1.1 mAb, prior to i.p. inoculation of B16 melanoma cells, resulted in an increased number of tumour cells in the PEC compared to NK cell non-depleted mice. Interestingly, the differences in tumour cell number between both groups were more prominent on days 7 and 14 than on day 3, which strongly suggested that early-infiltrating NK cells have a large influence on the subsequent anti-tumour response. The in vivo depletion of NK cells prior to immunization with melanoma cells abrogated the capacity of the spleen cells to generate CD8+ tumour-specific CTL after in vitro restimulation. This inability of generating anti-tumour CTL was partially restored by additional i.p. injections of recombinant IL-2 and/or IFN-gamma simultaneously with the immunization of melanoma cells. The in vitro depletion of NK cells prior to the in vitro restimulation with melanoma cells partially impaired the anti-tumour CTL generation from the spleen cells of the immunized mice. Lastly, the in vivo depletion of NK cells prior to immunization with melanoma cells abolished the protective immunity against melanoma cells at the rechallenge. Overall, these results indicate that early-appearing tumour-infiltrating NK cells not only participate in the anti-tumour early defence by themselves, but also play a crucial role in the generation of anti-tumour CTL.