T-regulatory cell modulation: the future of cancer immunotherapy?

T-regulatory cells suppress anti-tumour immunity in cancer patients and in murine tumour models. Furthermore, their activity is likely to have an effect on the effectiveness of immunotherapeutic treatments for cancer. Here we describe the current status of developing clinical strategies for modulating Treg activity in cancer patients

Looking Back and Looking Forward: Curriculum for Gifted and Talented Students

Curriculum for the gifted is guided by theories of differentiated learning that emphasize advanced content, challenging tasks, and interdisciplinary learning opportunities that differ from opportunities afforded to learners not identified as gifted. Guiding models in the field of curriculum for the gifted, including the Integrated Curriculum Model, the Schoolwide Enrichment Model, and the CLEAR Curriculum Model are discussed with relevant updates to the research incorporating these models. Additionally, advances in research instructional approaches recommended for gifted learners are discussed, including problem-based learning, STEM, online mentoring, and distance learning. The role of content standards is considered, and implications for continued research in curriculum and instruction for the gifted are examined

Late administration of murine CTLA-4 blockade prolongs CD8-mediated anti-tumor effects following stimulatory cancer immunotherapy

We have demonstrated that immunostimulatory therapies such as interleukin-2 (IL-2) and anti-CD40 (αCD40) can be combined to deliver synergistic anti-tumor effects. While this strategy has shown success, efficacy varies depending on a number of factors including tumor type and severe toxicities can be seen. We sought to determine whether blockade of negative regulators such as cytotoxic T lymphocyte antigen-4 (CTLA-4) could simultaneously prolong CD8(+) T cell responses and augment T cell anti-tumor effects. We devised a regimen in which anti-CTLA-4 was administered late so as to delay contraction and minimize toxicities. This late administration both enhanced and prolonged CD8 T cell activation without the need for additional IL-2. The quality of the T cell response was improved with increased frequency of effector/effector memory phenotype cells along with improved lytic ability and bystander expansion. This enhanced CD8 response translated to improved anti-tumor responses both at the primary and metastatic sites. Importantly, toxicities were not exacerbated with combination. This study provides a platform for rational design of immunotherapy combinations to maximize anti-tumor immunity while minimizing toxicities