Analysis of T-cell-receptor β-chain-gene usage in peripheral-blood and tumor-infiltrating lymphocytes from human non-small-cell lung carcinomas
✍ Scribed by Hamid Echchakir; Carine Asselin-Paturel; Guillaume Dorothee; Isabelle Vergnon; Dominique Grunenwald; Salem Chouaib; Fathia Mami-Chouaib
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 187 KB
- Volume
- 81
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Non-small-cell lung cancers (NSCLC) are often infiltrated by T lymphocytes. It is postulated that the presence of tumor-infiltrating lymphocytes (TIL) reflects a local host immune response against autologous tumors. To identify the nature of NSCLC TIL, we have characterized the molecular structure of the TCR chain expressed by infiltrating T cells and paired PBL from 9 untreated patients (4 LLC, 3 ADC and 2 SCC). For this purpose, we have used a high-resolution PCR-based method that determines CDR3 size patterns in TCRV sub-families in fresh tumors and their corresponding autologous PBL samples. Oligoclonality in T-cell populations was observed in 3 (Hor, Bla and Pub) out of 9 tumor biopsies analyzed. In contrast, the TCR repertoire of the 6 following patients as well as of all the autologous PBL was diverse, with virtually all V specificities expressed. Among the 3 tumors with dominant T-cell clonotypes, relative expansion of some T-cell sub-populations was observed. One patient (Hor) with significant TCRV21 expansion in tumor compared with autologous PBL, showed over-expression of a particular TCRV chain with unique V21-D-J2.7 junctional region not detected in autologous PBL. TCRV21/J2.7 expansion was also observed in IL-2-stimulated TIL cell lines and was confirmed by sequencing analysis of the V-D-J junctional region. These results strengthen the view that local antigen-driven selection may occur, and support the hypothesis that antitumor immune response may take place in some NSCLC. Int.