Nitta T, Bell R, Okumura K, Sato K, Steinman L
Department of Neurology and Genetics, Stanford University School of Medicine, California 94305.
Cancer Res. 1991 Oct 15;51(20):5565-9.
Expression of T-cell receptor (TCR) gene rearrangements in tumor-infiltrating lymphocytes (TILs) within primary and metastatic melanoma specimens was studied. In order to analyze TCR gene transcription in TILs within these tissues, we analyzed reverse transcribed complementary DNA from mRNA directly from tissues using the polymerase chain reaction. The polymerase chain reaction-amplified products were confirmed by dot or Southern blot hybridization with C alpha or C beta oligoprobes. First, we investigated the diversity of TCR V alpha and V beta gene usage in human malignant melanoma patients with multiple metastasis. We found in one patient, bearing multiple skin lesions, that the patterns of TCR V alpha and V beta repertoires in different sites of the skin (leg and chest wall) were almost the same. However, in another patient with skin and brain melanomas, different TCR repertoires were presented. Next, we examined the usage of murine TCR V beta genes in TILs within the primary and metastatic sites (liver, lung, and brain) of C57BL/6 mice bearing B16-F10 murine melanoma. The population of TILs in each primary and metastatic site expressed from one to four TCR V beta genes. In each metastatic site, the profile of TCR V beta gene expression was different. A different TCR V beta usage in TILs distributed within metastases of various organs may reflect differences in tumor antigenicity at these sites or may be due to differential homing patterns to these tumors.
研究了原发性和转移性黑色素瘤标本中肿瘤浸润淋巴细胞(TILs)中T细胞受体(TCR)基因重排的表达。为了分析这些组织中TILs的TCR基因转录情况,我们使用聚合酶链反应直接分析了来自组织mRNA的逆转录互补DNA。聚合酶链反应扩增产物通过与Cα或Cβ寡核苷酸探针的点杂交或Southern印迹杂交进行确认。首先,我们研究了多发转移的人类恶性黑色素瘤患者中TCR Vα和Vβ基因使用的多样性。我们在一名患有多处皮肤病变的患者中发现,皮肤不同部位(腿部和胸壁)的TCR Vα和Vβ库模式几乎相同。然而,在另一名患有皮肤和脑黑色素瘤的患者中,呈现出不同的TCR库。接下来,我们检查了携带B16-F10小鼠黑色素瘤的C57BL/6小鼠的原发性和转移部位(肝脏、肺和脑)中TILs的小鼠TCR Vβ基因的使用情况。每个原发性和转移部位的TILs群体表达1至4种TCR Vβ基因。在每个转移部位,TCR Vβ基因表达谱都不同。分布在各种器官转移灶中的TILs中不同的TCR Vβ使用情况可能反映了这些部位肿瘤抗原性的差异,或者可能是由于向这些肿瘤的归巢模式不同所致。