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 identify the nature of NSCLC TIL, we have characterized the molecular structure of the TCRbeta 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 TCRVbeta 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 Vbeta 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 TCRVbeta21 expansion in tumor compared with autologous PBL, showed over-expression of a particular TCRVbeta chain with unique Vbeta21-D-Jbeta2.7 junctional region not detected in autologous PBL. TCRVbeta21/Jbeta2.7 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 anti-tumor immune response may take place in some NSCLC.
Echchakir
H
H
Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 INSERM, Institut Gustave Roussy, Villejuif, France.
Asselin-Paturel
C
C
Dorothee
G
G
Vergnon
I
I
Grunenwald
D
D
Chouaib
S
S
Mami-Chouaib
F
F
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013268:Stimulation, Chemical
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta