CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rate ratio (HR). We found that 56.0 % of MPM tissues expressed CTLA-4 with variable intensity and percentage of positive cells estimated by the immunoreactive score. sCTLA-4 levels were significantly higher in sera (S-sCTLA-4) than in pleural effusions (PE-sCTLA-4) (geometric mean ratio = 2.70, P value = 0.020). CTLA-4 expression at the tissue level was higher in the epithelioid histological subtype than in the sarcomatoid, whereas at the serum level, it was higher in the sarcomatoid subtype. A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion. Interestingly, only the PE-sCTLA-4 was found to be a statistically significant positive prognostic factor (HR = 0.37, 95 % CI = 0.18-0.77, P value = 0.007). Indeed, PE-sCTLA-4 correlated with CTLA-4 expression in tissues, whereas this latter expression showed a weak association with OS. To confirm our findings, further experimental evidences obtained from a larger cohort of MPM patients are required. However, our results would indicate a positive correlation of PE-sCTLA-4 levels and OS in MPM patients.

Dijkgraaf-Witten theories are extended three-dimensional topological field theories of Turaev-Viro type. They can be constructed geometrically from categories of bundles via linearization. Boundaries and surface defects or interfaces in quantum field theories are of interest in various applications and provide structural insight. We perform a geometric study of boundary conditions and surface defects in Dijkgraaf-Witten theories. A crucial tool is the linearization of categories of relative bundles. We present the categories of generalized Wilson lines produced by such a linearization procedure. We establish that they agree with the Wilson line categories that are predicted by the general formalism for boundary conditions and surface defects in three-dimensional topological field theories that has been developed in [FSV].

Symmetries of three-dimensional topological field theories are naturally defined in terms of invertible topological surface defects. Symmetry groups are thus Brauer-Picard groups. We present a gauge theoretic realization of all symmetries of abelian Dijkgraaf-Witten theories. The symmetry group for a Dijkgraaf-Witten theory with gauge group a finite abelian group A, and with vanishing 3-cocycle, is generated by group automorphisms of A, by automorphisms of the trivial Chern-Simons 2-gerbe on the stack of A-bundles, and by partial e-m dualities. We show that transmission functors naturally extracted from extended topological field theories with surface defects give a physical realization of the bijection between invertible bimodule categories of a fusion category A and braided auto-equivalences of its Drinfeld center Z(A). The latter provides the labels for bulk Wilson lines; it follows that a symmetry is completely characterized by its action on bulk Wilson lines.

Abstract. We give a precise formulation of T -duality for Ramond-Ramond fields. This gives a canonical isomorphism between the "geometrically invariant" subgroups of the twisted differential K-theory groups associated to certain principal torus bundles. Our result combines topological T -duality with the Buscher rules found in physics.

In this paper we propose a "quantum reduction procedure" based on the reduction of algebras of differential operators on a manifold. We use these techniques to show, in a systematic way, how to relate the hydrogen atom to a family of quantum harmonic oscillators, by the means of the Kustaahneimo-Stiefel fibration.