Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

A comprehensive set of simulations of high-velocity collisions between main sequence stars

We report on a very large set of simulations of collisions between two main sequence (MS) stars. These computations were done with the ``Smoothed Particle Hydrodynamics'' method. Realistic stellar structure models for evolved MS stars were used. In order to sample an extended domain of initial parameters space (masses of the stars, relative velocity and impact parameter), more than 15000 simulations were carried out. We considered stellar masses ranging between 0.1 and 75 Msun and relative velocities up to a few thousands km/s. To limit the computational burden, a resolution of 2000-30000 particles per star was used. The primary goal of this study was to build a complete database from which the result of any collision can be interpolated. This allows us to incorporate the effects of stellar collisions with an unprecedented level of realism into dynamical simulations of galactic nuclei and other dense stellar clusters. We make the data describing the initial condition and outcome (mass and energy loss, angle of deflection) of all our simulations freely available on the Internet. We find that the outcome of collisions depends sensitively on the stellar structure and that, in most cases, using polytropic models is inappropriate. Published fitting formulas for the collision outcomes, established from a limited set of collisions, prove of limited use because they do not allow robust extrapolation to other stellar structures or relative velocities.Comment: 45 pages, 44 figures. Modified to reflect the changes in the published version (MNRAS). PDF version with high-res figures at http://obswww.unige.ch/~freitag/papers/article_collisions.pdf, simulation data at http://obswww.unige.ch/~freitag/MODEST_WG4/FB_Collision_Data/, movies at http://obswww.unige.ch/~freitag/collisions/animations/index.htm

Symbolic Computation of Polynomial Conserved Densities, Generalized Symmetries, and Recursion Operators for Nonlinear Differential-Difference Equations

Algorithms for the symbolic computation of polynomial conserved densities, fluxes, generalized symmetries, and recursion operators for systems of nonlinear differential-difference equations are presented. In the algorithms we use discrete versions of the Frechet and variational derivatives and the Euler and homotopy operators. The algorithms are illustrated for prototypical nonlinear polynomial lattices, including the Kac-van Moerbeke (Volterra) and Toda lattices. Results are shown for the modified Volterra and Ablowitz-Ladik lattices