Trials 11, 116C128 [PubMed] [Google Scholar] 32. with NKp30-Fc fusion protein or the addition of anti-Gal-3 antibody alone. Moreover, genetic down-regulation of Galectin-3 (shGal-3) resulted in tumor cells being more sensitive to NK cell lysis, and, reversely, Galectin-3-overexpressing HeLa cells HT-2157 (exGal-3) HT-2157 became less sensitive to NK cell killing. The results of these experiments were supported by studies in shGal-3-HeLa or exGal-3-HeLa xenograft non-obese diabetic/severe combined immunodeficiency mice after NK cell adoptive immunotherapy, indicating that Galectin-3 strongly antagonizes human NK cell attack against tumors (15) reported that the secretion of extracellular Gal-3 from tumor cells can activate apoptosis in both human and murine T cells after its binds to the cell surface glycoconjugate receptors Sema3b CD7 and CD29, providing new insight into the mechanism by which cancer cells escape the immune system. Wang and co-workers (11) further confirmed this conclusion in both humans and mice by showing that colorectal tumor-reactive T cells became apoptotic in response to Gal-3 stimulation, leading to enhanced tumor growth and (11). A human study also demonstrated that Gal-3 was down-regulated significantly in biopsies of inflamed tissue from inflammatory bowel disease patients. However, Gal-3 was expressed at comparably high levels in recovered inflammatory bowel disease patients. A genetic deficiency in Gal-3 rescued the apoptosis phenotype of the T cells and induced autoimmunity. In contrast, exogenous Gal-3 led to reduced proliferation of blood T cells. This finding illustrates that constitutive expression of epithelial Gal-3 may help to prevent inappropriate immune responses, providing solid evidence to support the hypothesis that Gal-3 is an immune regulator (16). On the basis of these findings, blockade approaches against Gal-3 have been explored. It has been reported that treatment with (18) found that HT-2157 TFD100, a glycopeptide from cod that binds Gal-3 with picomolar affinity, inhibited the apoptosis of activated T cells following induction with either recombinant Gal-3 or prostate cancer patient serum-associated Gal-3 at nanomolar concentrations. Collectively, Gal-3 may work as an immune regulator to induce apoptosis in activated T cells. Natural killer (NK) cells, which are effector lymphocytes of the innate immune system, provide the first line of defense against tumors. NK cells distinguish between normal healthy cells and abnormal cells using a sophisticated repertoire of cell surface receptors that control their activation, proliferation, and effect functions (19). For example, the natural cytotoxicity receptors (20), including NKp44 (21, 22), NKp46 (23), and NKp30 (24, 25), as well as NKG2D, are involved in the antitumor response (26, 27). Previous studies showed that Gal-3 is involved in the regulation of NK cell activation and function. Data from Dr. Gordana (41) demonstrated that Galectin-3-deficient mice are more resistant to lung metastases of malignant melanoma and that tumor-bearing Gal-3-deficient mice exhibit higher serum levels of IFN- and IL-17 than control tumor-bearing mice. Interestingly, in this model, the cytotoxic activity of splenic NK cells, but not cytotoxic T lymphocytes was greatly enhanced in Gal-3-deficient mice, suggesting that the NK cells of tumor-bearing mice are preferentially affected by Gal-3. In contrast with the Gal-3-induced apoptosis of T cells in antitumor immunity, the mechanism of Gal-3 inhibition in NK cell tumor immunity involves shielding the ligands on the tumor cells from NK cell-activating receptors. For example, the NK-activating receptor NKG2D is HT-2157 critical for tumor rejection after recognition of its tumor-associated ligand, major histocompatibility complex class I-related chain A (MICA). Gal-3 can bind the NKG2D binding site of MICA, which is expressed on the tumor cell surface, through the core two and for 5 min. The viruses in the supernatant were used to infect tumor cells. The knockdown HT-2157 efficiency was evaluated using Western blot and real-time RT-PCR analyses. The shRNA sequence targeting.