Galectin-1 expression confers immune privilege to tumor cells
Last Updated: March 24, 2004



NEW YORK (Reuters Health) - Galectin-1 expression by tumor cells
promotes their escape from T cell-dependent immunity, according to a
report in the March issue of Cancer Cell. The expression of galectin-
1 by various tumor types correlates with the aggressiveness of the
tumors and their acquisition of metastatic phenotypes, the authors
explain.


Dr. Gabriel A. Rabinovich from University of Buenos Aires in
Argentina and colleagues hypothesized that tumor cells tilt the
balance toward an immunosuppressive environment at the tumor site by
secreting galectin-1 and thereby escape the antitumor immune response.

The authors found high levels of galectin-1 expression in freshly
isolated tumors from human melanoma patients and in all six human and
murine melanoma cell lines tested.

Targeted inhibition of galectin-1 gene expression rendered mice
resistant to tumor challenge, the researchers note, and tumor
rejection induced by galectin-1 inhibition required intact CD4+ and
CD8+ T cell responses.

Selective blockade of galectin-1 synthesis in melanoma cells allowed
for the generation of a tumor-specific T1-type immune response that
provided resistance against subsequent challenge with galectin-1-
expressing tumors, the results indicate.

"We plan to test the role of galectin-1 in tumor immune escape in
other tumor types, such as lung, mammary and colon carcinomas," Dr.
Rabinovich told Reuters Health. "We also plan to explore in depth the
molecular mechanisms involved in this novel mechanism of tumor-immune
escape and to investigate the contribution of other members of the
galectin family to tumor immune privilege."

Several laboratories are investigating different types of synthetic
inhibitors of galectin-1 and other galectins, Dr. Rabinovich
explained. These agents "could block galectin-1-induced T-cell
apoptosis and inhibit other effects assigned to this protein, such as
tumor cell migration and cell adhesion in the context of the
extracellular matrix."

Dr. Rabinovich concluded, "The combination of different strategies --
stimulating both innate and adaptive immune response, but also
targeting negative regulatory pathways (and immune escape
mechanisms) -- will be necessary in the future to provide complete
antitumor protection and allow selective amplification of immune
responses for successful cancer immunotherapy."

He added, "I would like to point out that we are very proud and happy
that this work has been performed in our country even under the
difficult financial situation of the past few years."

The work was performed at the Hospital de Clinicas at the University
of Buenos Aires and at the Institute Leloir. All the research
investigators and fellows of the work are from CONICET (National
Research Council) and the work was supported mainly by grants from
Fundación Sales (Argentina), Fundación Antorchas (Argentina),
Ministry of Health (Argentina).





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