NDLI: Ras oncoproteins transfer from melanoma cells to T cells and modulate their effector functions.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lerenthal, Yaniv Schachter, Jacob Vernitsky, Helly Kloog, Yoel Besser, Michal J. Nagar, Meital Ehrlich, Marcelo Goldstein, Itamar Rainy, Nir Rechavi, Oded
Description	Country affiliation: Israel Author Affiliation: Vernitsky H ( Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.)
Abstract	Lymphocytes establish dynamic cell-cell interactions with the cells they scan. Previous studies show that upon cell contact, various membrane-associated proteins, such as Ras-family proteins, transfer from B to T and NK lymphocytes. Mutations in RAS genes that encode constitutively active, GTP-bound, oncoproteins are rather common in human cancers; for instance, melanoma. Cancer immunoediting has been postulated to contribute to the elimination of malignant melanoma. Thus, we asked whether Ras oncoproteins can transfer from melanoma to T cells, including tumor-infiltrating lymphocytes (TILs), and subsequently induce functional effects in the adopting T cells. To explore this issue, we genetically engineered an HLA-A2(+) melanoma cell line, MEL526, to express GFP or GFP-tagged H-Ras mutants stably. In this study, we show by an in vitro coculture system that GFP-tagged H-Ras, but not GFP, transfers from MEL526 to T cells and localizes to the inner aspect of their plasma membrane. This cell-contact-dependent process was increased by TCR stimulation and did not require strict Ag specificity. Importantly, we found a positive correlation between the levels of the acquired constitutively active H-RasG12V and ERK1/2 phosphorylation within the adopting TILs. We also show a significant increase in IFN-Î³ production and cytotoxic activity in TILs that acquired H-RasG12V compared to TILs that acquired a different H-Ras mutant. In conclusion, our findings demonstrate a hitherto unknown phenomenon of intercellular transfer of Ras oncoproteins from melanoma to TILs that consequently augments their effector functions.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Lymphocytes, Tumor-infiltrating Immunology Melanoma Metabolism Proto-oncogene Proteins P21(ras) Physiology T-lymphocytes Cell Line Coculture Techniques Pathology Primary Cell Culture Transfection Tumor Cells, Cultured Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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