Ostenstad B, Lea T, Schlichting E, Harboe M
Institute of Immunology and Rheumatology, Rikshospitalet, Oslo, Norway.
Gut. 1994 Mar;35(3):382-7. doi: 10.1136/gut.35.3.382.
This study investigated the phenotype of freshly isolated human tumour infiltrating lymphocytes (TIL) from 14 patients with colorectal tumours, and compared them with lymphocytes derived from the lamina propria of the unaffected mucosa and with lymphocytes derived from peripheral blood of the same patients. It was found that TIL expressed the activation markers CD25 and HLA-DR to a higher extent than the peripheral blood lymphocytes (p = 0.01), and that both lamina propria lymphocytes and TIL preferentially expressed the CD45RO + phenotype, associated with memory cells, in contrast with peripheral blood lymphocytes [corrected]. Both lamina propria lymphocytes and TIL contained few natural killer (NK) cells (CD3-CD56+) compared with peripheral blood lymphocytes (p = 0.001), and this was reflected in the cytotoxicity assays. After 1 to 2 weeks in culture with interleukin-2 100 U/ml, lymphocytes from all three compartments had a high cytolytic activity against all targets tested, consistent with the lymphokine activated killer cell phenomenon. No increase in the number of NK cells was noted after culture, but 20-30% of the T cells now coexpressed the CD56 molecule. This was most prominent in the CD8+ subset, but lymphokine activated killer cell activity was found in both CD4+ and CD8+ subsets. Possible tumour escape mechanisms are discussed.
本研究调查了14例结直肠肿瘤患者新鲜分离的人肿瘤浸润淋巴细胞(TIL)的表型,并将其与来自未受影响黏膜固有层的淋巴细胞以及来自同一患者外周血的淋巴细胞进行比较。结果发现,TIL比外周血淋巴细胞更高度地表达活化标志物CD25和HLA - DR(p = 0.01),并且固有层淋巴细胞和TIL均优先表达与记忆细胞相关的CD45RO +表型,这与外周血淋巴细胞不同[校正后]。与外周血淋巴细胞相比,固有层淋巴细胞和TIL中自然杀伤(NK)细胞(CD3 - CD56 +)很少(p = 0.001),这在细胞毒性试验中得到反映。在含有100 U/ml白细胞介素-2的培养基中培养1至2周后,来自所有三个区室的淋巴细胞对所有测试靶标均具有高细胞溶解活性,这与淋巴因子激活的杀伤细胞现象一致。培养后未观察到NK细胞数量增加,但现在20 - 30%的T细胞共表达CD56分子。这在CD8 +亚群中最为明显,但在CD4 +和CD8 +亚群中均发现了淋巴因子激活的杀伤细胞活性。文中讨论了可能的肿瘤逃逸机制。