Kralovske Vinohrady University Hospital, Prague, Czech Republic;
Faculty of Science, Charles University, Prague, Czech Republic.
Anticancer Res. 2023 Feb;43(2):631-638. doi: 10.21873/anticanres.16199.
BACKGROUND/AIM: Melanoma is a skin cancer without effective therapy, showing high immunogenicity and mostly partial spontaneous regression (SR). The exact mechanisms of SR are still not well understood; therefore, the use of animal melanoma models is necessary to unravel the immunological processes during SR.
Skin melanoma samples (n=57) and peripheral blood samples (n=57) from the same animals were collected. Melanoma-bearing Libechov Minipigs (MeLiM) aged 3, 4, 6, 8, 10, 12, 20, and 32 weeks were used, and samples were analysed by flow cytometry for detection of immune cell subpopulations.
The proportion of CD3-CD8+ (NK) cells in melanoma samples was found to be higher compared to blood samples at 6-8 weeks of age and then at 12 weeks of age. The population of CD4+CD8+ (effector/memory T helper) cells and CD4-CD8+ (cytotoxic T and NK) cells was also increased in melanoma compared to blood samples in 10-32-week-old pigs. The proportion of CD4-CD8+ cells in melanoma samples, then augmented until the 32 week. On the contrary, the proportion of CD4+CD8- (naive T helper) cells was lower in melanoma samples versus blood samples in 6-32-week-old animals.
Cytotoxic T cells were the most abundant population of tumour infiltrating immune cells found in MeLiM melanomas of animals aged 10-32 weeks, probably causing the destruction of melanoma cells. Furthermore, the development of specific (adaptive) immune response represented mainly by cytotoxic T cells seems to be crucial for the successful SR of porcine melanoma.
背景/目的：黑色素瘤是一种无有效治疗方法的皮肤癌，表现出高免疫原性，且大多为部分自发消退（SR）。SR 的确切机制尚不清楚；因此，有必要使用动物黑色素瘤模型来揭示 SR 过程中的免疫过程。
收集了来自同一动物的皮肤黑色素瘤样本（n=57）和外周血样本（n=57）。使用了年龄为 3、4、6、8、10、12、20 和 32 周的携带黑色素瘤的利比希猪（MeLiM），并通过流式细胞术分析这些样本，以检测免疫细胞亚群。
与血液样本相比，6-8 周龄和 12 周龄时黑色素瘤样本中的 CD3-CD8+（NK）细胞比例较高。与 10-32 周龄猪的血液样本相比，黑色素瘤样本中 CD4+CD8+（效应/记忆 T 辅助）细胞和 CD4-CD8+（细胞毒性 T 和 NK）细胞的数量也增加了。黑色素瘤样本中 CD4-CD8+细胞的比例也增加，直到第 32 周。相反，与 6-32 周龄动物的血液样本相比，黑色素瘤样本中 CD4+CD8-（幼稚 T 辅助）细胞的比例较低。
在 10-32 周龄动物的 MeLiM 黑色素瘤中，细胞毒性 T 细胞是肿瘤浸润免疫细胞中最丰富的群体，可能导致黑色素瘤细胞的破坏。此外，由细胞毒性 T 细胞代表的特异性（适应性）免疫反应的发展似乎对猪黑色素瘤的成功 SR 至关重要。
