Home > News > MHC-restricted phosphopeptides derived from Insulin receptor substrate-2 and CDC25b offer broad-based immunotherapeutic agents for cancer

MHC-restricted phosphopeptides derived from Insulin receptor substrate-2 and CDC25b offer broad-based immunotherapeutic agents for cancer

Cancer cells display novel phosphopeptides in association with MHC class I and II molecules. In this study, we evaluated two HLA-A2-restricted phosphopeptides derived from the insulin receptor substrate (IRS)-2 and the cell cycle regulator CDC25b. These proteins are both broadly expressed in multiple malignancies and linked to cancer cell survival. Two phosphopeptides, termed pIRS-21097-1105 and pCDC25b38-46, served as targets of strong and specific CD8 T-cell memory responses in normal human donors. We cloned T-cell receptor (TCR) cDNAs from murine CD8 T-cell lines specific for either pIRS-21097-1105 or pCDC25b38-46. Expression of these TCR in human CD8 T-cells imparted high-avidity phosphopeptide-specific recognition and cytotoxic and cytokine-secreting effector activities. Using these cells, we found that endogenously processed pIRS-21097-1105 was presented on HLA-A2+ melanomas and breast, ovarian, and colorectal carcinomas. Presentation was correlated with the level of the Ser1100-phosphorylated IRS-2 protein in metastatic melanoma tissues. The highest expression of this protein was evident on dividing malignant cells. Presentation of endogenously processed pCDC25b38-46 was narrower, but still evident on HLA-A2+ melanoma, breast carcinoma and lymphoblastoid cells. Notably, pIRS-21097-1105-specific and pCDC25b38-46-specific TCR-expressing human CD8 T-cells markedly slowed tumor outgrowth in vivo. Our results define two new antigens that may be developed as immunotherapeutic agents for a broad range of HLA-A2+ cancers.

Does caffeine fight cancer?

Epidemiological studies have shown that caffeinated drinks may help prevent skin cancer by inhibiting a DNA repair pathway, thus killing potentially precancerous cells. In English, it means that drinking drinks containing caffeine will reduce one’s chances of developing some types of cancer, including UV-associated skin cancer. That just proves that caffeine fight cancer. The results, published in the Proceedings of the National Academy of Sciences, lend support to the idea that caffeine could be added to sunblock to increase its protective effects. At the cellular level, they’re showing that caffeine is working in this way of inducing an apoptotic mechanism. This statement was then made by cancer epidemiologist Joanne Kotsopoulos of the University of Toronto.

In the 2007, a study stated that woman who drank caffeinated coffee on a daily basis had a 10 percent lower risk of nonmelanoma skin cancer. Six or more cups of coffee a day translated to a 30 percent reduction in risk. Mouse studies have also confirmed the link, with both ingested and topically-applied caffeine lowering skin cancer rates in the animals. But exactly how the stimulant protected against cancer remained mysterious. One possibility is the drug’s inhibition of ataxia telangiectasia and Rad3-related (ATR), a large protein kinase that senses incomplete DNA replication often a result of DNA damage and signals the cell to not divide. By inhibiting ATR activity, caffeine could make cells more likely to die in response to UV damage, preventing damaged cells from ever becoming cancerous.

Studies have shown that the caffeine molecule acts as a sunscreen. It therefore blocks the penetration of UV rays. And that is why today we see many sunblocks with a good amount of caffeine in them.

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Can sugar consumption cause breast cancer?

A recent study stated that drinking three sugar sweetened drinks a week would increase the risk of having breast cancer. The study had 776 pre-menopausal women and 779 post-menopausal women. Each women’s breast density was assessed by examining their mammograms. The women were told to make a note of sweet they consumed such as chocolates, cakes, ice cream or any sweet drinks. Also they were asked to make a note of how much of spoonful of sugar they add to the drinks.

It was then found out that post-menopausal women who consumed more of sugar, an increase in the density of breast. While the pre-menopausal women observed an increase in breast density when they consumed sugar food. These women, in a week were just consuming three sugar sweetened drinks. The study then further stated that sugar tends to increase the migration of breast cells together. This explains the fact that the premenopausal women who consumed sugar-sweetened drinks were 3 percent more likely to have dense breasts than those who didn’t consume the drinks. And having dense breasts increases your risk of breast cancer by making it difficult to see tumors on mammograms.

However, there is more to be studied on this matter. But until then there is still a link between the sugar consumption and breast density. About 40% of women in the US have dense breast and they are totally unaware of it. Doctors say that women with a dense breast are five time more likely to have a breast cancer and 10 times more likely to miss the tumor in the mammogram test.

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