Vose B M, Gallagher P, Moore M, Schofield P F
Br J Cancer. 1981 Dec;44(6):846-55. doi: 10.1038/bjc.1981.283.
The cytotoxic activity of peripheral-blood (PBL), lymph-node (LNC) and tumour-infiltrating lymphocytes (TIL) from 47 patients undergoing surgery for colon carcinoma (Duke's Stage A, 1 patient; B, 24; C, 15 and C with metastases, 7) was examined in short-term 51Cr-release assays, against fresh autologous tumour cells, allogeneic colon cancer cells and the erythroleukaemia cell line, K562. Cytotoxicity against autologous cells was detected in at least one effector population in 23/47 patients (49%), with overall frequencies which did not differ for patients in different Duke's stages of disease. By contrast, lysis of allogeneic tumour cells was infrequent (11%) regardless of the effector population to which they were exposed. Cytotoxicity against K562, cells highly sensitive to NK activity, though variable, was detected in 93% of PBL of normal donors and 83% of patients, and among the latter showed no evidence of significant decline with advancing disease. However, LNC and TIL anti-K562 activity was infrequent (17%) in concordance with previous reports. There was no correlation between the ability of patients' PBL to lyse autologous tumour and K562 cells. The independence of these 2 cytotoxic actions was further explored in studies fractionating lymphocytes: autologous tumour killing was augmented in T-enriched PBL; whereas the greatest anti-K562 activity was found in the corresponding non-T fraction. Lymphocyte cytotoxicity in colonic neoplasia is thus manifest in 2 apparently independent lymphocyte populations; a relatively specific killer T-cell population, detectable in PBL, LNC and TIL, which is preferentially reactive with the autologous cells; and a non-specific killer population, largely limited to PBL, with the properties of NK cells. The activity of neither population reflects the clinical status of patients with this disease.
对47例接受结肠癌手术的患者(杜克分期A期1例、B期24例、C期15例、伴转移的C期7例)的外周血淋巴细胞(PBL)、淋巴结淋巴细胞(LNC)和肿瘤浸润淋巴细胞(TIL)的细胞毒性活性进行了检测,采用短期⁵¹Cr释放试验,以新鲜自体肿瘤细胞、同种异体结肠癌细胞和红白血病细胞系K562为靶细胞。在23/47例患者(49%)的至少一种效应细胞群体中检测到对自体细胞的细胞毒性,不同杜克分期疾病患者的总体频率无差异。相比之下,无论暴露于何种效应细胞群体,对同种异体肿瘤细胞的裂解都很少见(11%)。对K562细胞(对NK活性高度敏感)的细胞毒性虽然存在差异,但在93%的正常供体PBL和83%的患者中检测到,在后者中未显示出随着疾病进展而显著下降的证据。然而,与先前报道一致,LNC和TIL的抗K562活性很少见(17%)。患者PBL裂解自体肿瘤和K562细胞的能力之间没有相关性。在淋巴细胞分级分离研究中进一步探讨了这两种细胞毒性作用的独立性:富含T细胞的PBL中自体肿瘤杀伤作用增强;而最大的抗K562活性则在相应的非T细胞组分中发现。因此,结肠肿瘤中的淋巴细胞细胞毒性表现在2个明显独立的淋巴细胞群体中;一个相对特异性的杀伤性T细胞群体,可在PBL、LNC和TIL中检测到,优先与自体细胞反应;以及一个非特异性杀伤群体,主要限于PBL,具有NK细胞的特性。这两种群体的活性均不能反映该疾病患者的临床状态。