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在病灶内注射卡介苗后增强10号线肿瘤免疫过程中主要组织相容性复合体II类抗原的表达

Major histocompatibility complex class II antigen expression during potentiation of line-10 tumor immunity after intralesional administration of bacillus Calmette-Guérin.

作者信息

Steerenberg P A, De Jong W H, Geerse E, Aleva B J, Besselink C M, Van Rens B T, Rutten V P, Poels L G, Scheper R J, Den Otter W

机构信息

Laboratory for Pathology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.

出版信息

Cancer Immunol Immunother. 1990;32(2):95-104. doi: 10.1007/BF01754205.

Abstract

Intralesional injection of BCG into an established line-10 hepatocellular carcinoma in the strain-2 guinea pig causes regression of the tumor and induction of line-10 immunity. We found that the animals were already protected for a second challenge with line-10 tumor cells 7 days after BCG treatment. We studied whether this early induction of immunity was correlated with the expression of MHC class II antigens on line-10 tumor cells and was correlated with an increased expression of MHC class II antigens on leukocytes in the primary tumor and in the regional lymph node (Ln. axillaris accessorius). The MHC class II antigens and the leukocyte subpopulations were measured with monoclonal antibodies and flow cytofluorometry. In the draining lymph node the number of nucleated cells increased about 10-fold during the first 5 days after intralesional injection of BCG. At this time the MHC class II antigen expression of these cells was increased from 21%-32% in the naive controls to 39%-53% in animals with BCG-treated tumors. This implies that the number of MHC-class-II-positive cells increased about 20-fold in the draining lymph node. Surprisingly, the increase in percentage of MHC-class-II-antigen-positive cells was mainly due to an increase of IgM-positive B cells from 8%-11% to 22%-41% and an increase of IgG-positive B cells from 7%-27% to 25%-44%. In the tumor, BCG treatment induced a small increase of MHC-class-II-antigen-positive cells from 11%-12% to 15%-20%. Probably this increase came not from tumor cells but mainly from a BCG-induced infiltration of mononuclear cells, as an increase of T cells from 14% to 20%, an increase of macrophages from 8% to 18%, and an increase of B cells from 0 to 6% was observed. We conclude that the potentiation of anti-(line-10 tumor cell) immunity correlated with a 20-fold increase of MHC-class-II-antigen-positive cells in the lymph nodes and a small increase in the number of MHC-class-II-antigen-positive tumor-infiltrating cells.

摘要

向2系豚鼠已建立的10号线肝细胞癌病灶内注射卡介苗可使肿瘤消退并诱导产生10号线免疫。我们发现,卡介苗治疗7天后,动物对再次接种10号线肿瘤细胞已有保护作用。我们研究了这种早期免疫诱导是否与10号线肿瘤细胞上MHC II类抗原的表达相关,以及是否与原发肿瘤和区域淋巴结(腋副淋巴结)中白细胞上MHC II类抗原表达的增加相关。用单克隆抗体和流式细胞荧光术检测MHC II类抗原和白细胞亚群。在病灶内注射卡介苗后的前5天,引流淋巴结中有核细胞数量增加了约10倍。此时,这些细胞的MHC II类抗原表达从未处理对照组的21% - 32%增加到卡介苗治疗肿瘤动物的39% - 53%。这意味着引流淋巴结中MHC II类阳性细胞数量增加了约20倍。令人惊讶的是,MHC II类抗原阳性细胞百分比的增加主要是由于IgM阳性B细胞从8% - 11%增加到22% - 41%,以及IgG阳性B细胞从7% - 27%增加到25% - 44%。在肿瘤中,卡介苗治疗使MHC II类抗原阳性细胞从11% - 12%略有增加至15% - 20%。这种增加可能并非来自肿瘤细胞,而是主要源于卡介苗诱导的单核细胞浸润,因为观察到T细胞从14%增加到20%,巨噬细胞从8%增加到18%,B细胞从0增加到6%。我们得出结论,抗(10号线肿瘤细胞)免疫的增强与淋巴结中MHC II类抗原阳性细胞增加20倍以及肿瘤浸润的MHC II类抗原阳性细胞数量略有增加相关。

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