Analysis of T-cell-receptor beta-chain-gene usage in peripheral-blood and tumor-infiltrating lymphocytes from human non-small-cell lung carcinomas

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 identi fy the nature of NSCLC TIL, we have characterized the molecular structure o f the TCR beta 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 us ed a high-resolution PCR-based method that determines CDR3 size patterns in TCRV beta sub-families in fresh tumors and their corresponding autologous PBL samples. Oligoclonality in T-cell populations was observed in 3 (Hor, B la and Pub) out of 9 tumor biopsies analyzed. In contrast, the TCR repertoi re of the 6 following patients as well as of all the autologous PBL was div erse, with virtually all V beta specificities expressed. Among the 3 tumors with dominant T-cell clonotypes, relative expansion of some T-cell sub-pop ulations was observed. One patient (Hor) with significant TCRV beta 21 expa nsion in tumor compared with autologous PBL, showed over-expression of a pa rticular TCRV beta chain with unique V beta 21-D-J beta 2.7 junctional regi on not detected in autologous PBL. TCRV beta 21/J beta 2.7 expansion was al so observed in IL-2-stimulated TIL cell lines and was confirmed by sequenci ng analysis of the V-D-J junctional region. These results strengthen the vi ew that local antigen-driven selection may occur, and support the hypothesi s that antitumor immune response may take place in some NSCLC, Int. J. Canc er 81:205-213, 1999, (C) 1999 Wiley-Liss, Inc.