New insight into how tumors evade the immune system

A new research study sheds light on how cancer cells manage to evade the immune system despite the presence of tumor-specific immune cells. The researchers found that mouse and human melanoma cells secrete galectin-1, which has a negative impact on the survival of T cells, and that inhibition of Gal-1 dramatically reduces tumor formation in mice. The research has exciting implications for future anticancer therapies that may stimulate an effective immune response against tumor cells.

Tumor cells enhance their own survival by somehow escaping attacks from the immune system of the host. A molecule called galectin-1 (Gal-1) has a negative influence on immune cells called T cells and is present in many different tumor types, especially aggressive cancers like prostate, colon, and ovarian carcinomas and melanoma. Dr. Gabriel A. Rabinovich from the University of Buenos Aires in Argentina and colleagues designed a study to look at how Gal-1 may contribute to the interaction between tumor cells and the host environment. The researchers found that mouse and human melanoma cells secrete Gal-1and demonstrated that Gal-1 has a negative impact on the survival of T cells. Further, inhibition of Gal-1 can dramatically reduce tumor formation in mice challenged with cancer cells.

The researchers conclude that Gal-1-dependent mechanisms play a critical role in the ability of tumors to overwhelm cancer-fighting T cells. “Our results show that Gal-1 contributes to immune privilege of tumors by modulating survival and/or polarization of effector T cells, providing the first concrete evidence of a link between the immunoregulatory properties of this protein and its contribution to tumor progression. More importantly, our data highlight a novel molecular target for manipulation of T cell tolerance and cell death with profound implications for cancer immunotherapy,” explains Dr. Rabinovich.

Natalia Rubinstein, Mariano Alvarez, Norberto W. Zwirner, Marta A. Toscano, Juan M. Ilarregui, Alicia Bravo, José Mordoh, Leonardo Fainboim, Osvaldo L. Podhajcer, and Gabriel A. Rabinovich: “Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection: A potential mechanism of tumor-immune privilege”

Published in Cancer Cell, Volume 5, Number 3, March 2004, pages 241-252.

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