Human Ovarian Tumor Cells Escape γδ T Cell Recognition Partly by Down Regulating Surface Expression of MICA and Limiting Cell Cycle Related Molecules

Background: Mechanisms of human Vc2Vd2 T cell-mediated tumor immunity have yet to be fully elucidated. Methods and Findings: At least some tumor cell recognition is mediated by NKG2D-MICA interactions. Herein, by using MTT assay and PI-BrdU co-staining and Western-blot, we show that these Vc2Vd2 T cells can limit the proliferation of ovarian tumor cells by down regulation of apoptosis and cell cycle related molecules in tumor cells. Cell-to-cell contact is critical. cd T cell-resistant, but not susceptible ovarian tumor cells escape cd T cell-mediated immune recognition by up-regulating pErk1/2, thereby decreasing surface MICA levels. Erk1/2 inhibitor pretreatment or incubation prevents this MICA decrease, while up-regulating key cell cycle related molecules such as CDK2, CDK4 and Cyclin D1, as well as apoptosis related molecules making resistant tumor cells now vulnerable to cd T cell-mediated lysis. Conclusion: These findings demonstrate novel effects of cdT cells on ovarian tumor cells

Endogenous Sanctioning Institutions and Migration Patterns: Experimental Evidence

This is the author accepted manuscriptWe experimentally analyze the e ect of the endogenous choice of sanctioning institutions on cooperation and migration patterns. Subjects are assigned to one of two groups, are endowed with group-speci c preferences, and play a public goods game. We compare an environment in which subjects can move between groups and vote on whether to implement sanctions, to one in which only one group is exogenously endowed with sanctions. We nd that the possibility of voting leads to a more e cient partition of subjects across groups, higher payo s, lower inequality, and lower migration rates. Over time, subjects tend to vote for institutions

Alexithymia, Immunity and Cervical Intraepithelial Neoplasia: Replication

Background: In a previous study [Psychother Psychosom 1994;61:199-204] we investigated the relationship between alexithymia, carcinogenesis and immunity in a group of women who were unconscious sufferers from precancerous lesions of the cervix (CIN). The results of this study showed a high level of association between alexithymia and CIN and, an even more interesting fact, between alexithymia and reduced levels of immunity. Methods: The aim of the present study is to check the results of the previous one by testing a larger group (43 women affected by cervical dysplasia and 67 healthy women) and by the use of a self-administered test for detection of alexithymia, the well-validated Twenty-Item Toronto Alexithymia Scale (TAS-20). Results: The results confirm that women suffering from CIN have higher average TAS-20 ratings (55) than normal women (47.32) and that the level of alexithymia detected in the group of women suffering from dysplasia (42.5%) is higher than that of normal women (12.85%). Moreover, the present study confirms that alexithymic women have lower rates of a number of lymphocyte subsets than non-alexithymic women. Conclusions: This study fully confirms the results of our previous work and those of a number of other studies: (1) personality might be one of the factors jointly responsible for the outbreak of cancer; (2) the immune system appears to play an important part as a mediator between personality and cancer

Pancreas-After-Islet Transplantation in Nonuremic Type 1 Diabetes: A Strategy for Restoring Durable Insulin Independence.

Islet transplantation offers a minimally invasive approach for β cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet reinfusions from distinct donors, increasing the risk of allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the United States; however, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear. We describe a case series of seven patients undergoing solid organ pancreas transplant following islet graft failure with long-term follow-up of pancreatic graft survival and renal function. Despite highly variable panel reactive antibody levels prior to pancreas transplant (mean 27 ± 35%), all seven patients achieved stable and durable insulin independence with a mean follow-up of 6.7 years. Mean hemoglobin A1c values improved significantly from postislet, prepancreas levels (mean 8.1 ± 1.5%) to postpancreas levels (mean 5.3 ± 0.1%; p = 0.0022). Three patients experienced acute rejection episodes that were successfully managed with thymoglobulin and methylprednisolone, and none of these preuremic type 1 diabetic recipients developed stage 4 or 5 chronic kidney disease postoperatively. These results support pancreas-after-islet transplantation with aggressive immunosuppression and protocol biopsies as a viable strategy to restore insulin independence after islet graft failure