No abstract

Patients with head and neck squamous cell carcinoma harbor T-cell inflamed and non-T-cell inflamed tumors. Despite this, only 20% of patients respond to checkpoint inhibitor immunotherapy. Lack of induction of innate immunity through pattern-recognition receptors such as the stimulator of interferon (IFN) genes (STING) receptor may represent a significant barrier to the development of effective antitumor immunity. Here, we demonstrate robust control of a T-cell inflamed (MOC1), but not non-T-cell inflamed (MOC2), model of head and neck cancer by activation of the STING pathway with the synthetic cyclic dinucleotide RP,RP dithio-c-di-GMP. Rejection or durable tumor control of MOC1 tumors was dependent upon a functional STING receptor and CD8 T lymphocytes. STING activation resulted in increased tumor microenvironment type 1 and type 2 IFN and greater expression of PD-1–pathway components in vivo. Established MOC1 tumors were rejected and distant tumors abscopally controlled, after adaptive immune resistance had been reversed by the addition of PD-L1 mAb. These findings suggest that PD-1-pathway blockade may reverse adaptive immune resistance following cyclic dinucleotide treatment, enhancing both local and systemic antitumor immunity.

We present a novel algorithm to perform continuous collision detection for articulated models.

No abstract

We present a fast continuous collision detection (CCD) algorithm for articulated models using Taylor models and temporal culling. Our algorithm is a generalization of conservative advancement (CA) from convex models [Mirtich 1996] to articulated models with non-convex links. Given the initial and final configurations of a moving articulated model, our algorithm creates a continuous motion with constant translational and rotational velocities for each link, and checks for interferences between the articulated model under continuous motion and other models in the environment and for self-collisions. If collisions occur, our algorithm reports the first time of contact (TOC) as well as collision witness features. We have implemented our CCD algorithm and applied it to several challenging scenarios including locomotion generation, articulated-body dynamics and character motion planning. Our algorithm can perform CCDs including self-collision detection for articulated models consisting of many links and tens of thousands of triangles in 1.22 ms on average running on a 3.6 GHz Pentium 4 PC. This is an improvement on the performance of prior algorithms of more than an order of magnitude.