Cizkova Jana, Sinkorova Zuzana, Strnadova Kristyna, Cervinkova Monika, Horak Vratislav, Sinkora Jiri, Stepanova Katerina, Sinkora Marek
Laboratory of Applied Proteome Analyses, Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Libechov, Czech Republic; Laboratory of Tumor Biology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Libechov, Czech Republic; Department of Veterinary Sciences, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences, Prague, Czech Republic.
Department of Radiobiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
Dev Comp Immunol. 2019 Mar;92:60-68. doi: 10.1016/j.dci.2018.10.001. Epub 2018 Oct 9.
Using a porcine model, we describe Melanoma-Associated CD4CD8 T-lymphocytes (MATL) in peripheral blood that increase during melanoma regression. These MATL possess the CD4CD8 phenotype and they have their direct counterparts in Tumor Infiltrating Lymphocytes (TIL) isolated from melanoma loci. Both MATL and CD4CD8 TIL have a similar expression of selected markers indicating that they represent effector/memory αβ T-cell subset. Moreover, although TIL also contain CD4CD8 T-cells, only CD4CD8 TIL expand during melanoma regression. Importantly, TIL isolated from different pigs and different melanoma loci among the same pig have similar composition of CD4/CD8 subsets, indicating that the composition of the MATL and TIL compartment is identical. Analysis of sorted cells from regressing pigs revealed a unique MATL subpopulation with mono-specific T-cell receptor that was further analyzed by sequencing. These results indicate that pigs regressing melanomas possess a characteristic population of recirculating T-cells playing a role in tumor control and regression.
利用猪模型,我们描述了外周血中与黑色素瘤相关的CD4CD8 T淋巴细胞(MATL),其在黑色素瘤消退过程中数量增加。这些MATL具有CD4CD8表型,并且在从黑色素瘤位点分离出的肿瘤浸润淋巴细胞(TIL)中有直接对应的细胞。MATL和CD4CD8 TIL对所选标志物具有相似的表达,表明它们代表效应/记忆αβ T细胞亚群。此外,虽然TIL中也含有CD4CD8 T细胞,但只有CD4CD8 TIL在黑色素瘤消退过程中扩增。重要的是,从不同猪以及同一头猪的不同黑色素瘤位点分离出的TIL具有相似的CD4/CD8亚群组成,表明MATL和TIL区室的组成是相同的。对消退期猪的分选细胞进行分析,发现了一个具有单特异性T细胞受体的独特MATL亚群,并通过测序对其进行了进一步分析。这些结果表明,黑色素瘤消退的猪拥有一群具有特征性的循环T细胞,它们在肿瘤控制和消退中发挥作用。