Restored T-cell activation mechanisms in human tumour-infiltrating lymphocytes from melanomas and colorectal carcinomas after exposure to interleukin-2 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-01

AUTHORS

F De Paola, R Ridolfi, A Riccobon, E Flamini, F Barzanti, A M Granato, G L Mordenti, L Medri, P Vitali, D Amadori

ABSTRACT

We investigated the effects of interleukin-2 (IL-2) exposure on T-cell signal transduction molecules and apoptosis markers in tumour-infiltrating lymphocytes (TIL) isolated from 20 melanoma and 16 colorectal carcinoma metastases and expanded in vitro for therapeutic reinfusion. Before IL-2 culture, TIL showed undetectable or very low levels of T-cell receptor (TCR) epsilon chain, p56(lck), Fas ligand (FasL) and Bax expression, while Bcl-2 values were elevated. Cancer cells were characterised by low or absent Fas and Bcl-2 and high Bax expression. Notably, they also expressed FasL. After 41-48 days of IL-2 culture, TCR epsilon chain and p56(lck) expression of TIL rose to median values of approximately 80 and 30% positive cells, respectively (P<0.001), FasL expression was detected in 45% cells from melanomas (P<0.001) and in 3% from colorectal carcinomas (P=0.09), and Bax-positive cells increased from 17.5 to 70% (P=0.005). Moreover, TCR zeta chain-positive cells were significantly increased from baseline (P=0.001), Bcl-2-positive cells dropped from 50 to 1% (P=0.007) and perforin content was high, while Fas expression was not significantly modified by IL-2 culture. In conclusion, our data suggest that the degree of immunosuppression in TIL from melanomas and colorectal carcinomas is very high, and the apoptosis markers' repertoire of cancer cells resembles that of immune-privileged tissue. Interleukin-2 culture appears to restore lymphocyte activation mechanisms, resulting in consistent FasL expression and perforin production. More... »

PAGES

320

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6600679

DOI

http://dx.doi.org/10.1038/sj.bjc.6600679

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049567588

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12610520


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