The Administrative Part of Core A provides Dr. Schreiber protected time for scientific leadership and careful guidance of the Program Project. This leadership will be essential for achieving the goals of the program project that depend on integrating scientists with highly complementary but fundamentally different skills and operation modes and very diverse methodology and technology. Effective productive integration will depend on minimizing negative effects of the physical separation of the interacting scientists. This requires dedicated time from Dr. Schreiber for careful planning and using methods of easy interaction over long distances. For coordinating the scientific and technical activities of this program project, the Core will (i) organize a monthly steering committee meeting and research-in-progress meeting with the leaders of the four projects, the statistician and the core directors with careful planning of the agenda including distribution of data, manuscripts and papers to be discussed, (ii) organizes a more comprehensive quarterly meeting of all scientific and technical personnel involved in the program, (iii) prepare, distribute and maintain electronic files of reports, protocols and images and distribute relevant research articles, (iv) prepare and update existing databases for cell lines, gene constructs, monoclonal antibodies and vectors, and (v) monitor day-today expenses, support and organize the visits of one external scientific advisor and one external collaborator per year. The Statistics Part of Core A, provides a protected time to our statistician Dr. Karrison. This provides researchers with a highly experienced scholarly statistician who is dedicated to the success of this program project. This arrangement will give us much improved access to biostatistical consultation during the planning and execution and analysis stages of the proposed studies. The Imaging Part of Core A under the leadership of Dr. P. Charles Lin provides researchers with continued access to the first rate imaging institute at Vanderbilt for optical imaging using window chamber technology. The migration and localization of the fluorescent T cells or fluorochrome-tagged molecules to large well-established tumors will be monitored through a window opening on one side of these tumors using the Zeiss multiphoton laser scanning microscope LSM 510 META. The new META (Zeiss) spectral detectors resolve emissions from these different fluorescent dyes efficiently and exactly by providing linear spectral unmixing using specialized software. The microscopic imaging of the tumor microenvironment will give us detailed information on real time events and precise locality of cells or molecules injected into mice in the various models proposed.
| Arina, Ainhoa; Karrison, Theodore; Galka, Eva et al. (2017) Transfer of Allogeneic CD4+ T Cells Rescues CD8+ T Cells in Anti-PD-L1-Resistant Tumors Leading to Tumor Eradication. Cancer Immunol Res 5:127-136 |
| Kammertoens, Thomas; Friese, Christian; Arina, Ainhoa et al. (2017) Tumour ischaemia by interferon-? resembles physiological blood vessel regression. Nature 545:98-102 |
| Tang, Haidong; Zhu, Mingzhao; Qiao, Jian et al. (2017) Lymphotoxin signalling in tertiary lymphoid structures and immunotherapy. Cell Mol Immunol 14:809-818 |
| Arina, Ainhoa; Idel, Christian; Hyjek, Elizabeth M et al. (2016) Tumor-associated fibroblasts predominantly come from local and not circulating precursors. Proc Natl Acad Sci U S A 113:7551-6 |
| Blankenstein, Thomas; Leisegang, Matthias; Uckert, Wolfgang et al. (2015) Targeting cancer-specific mutations by T cell receptor gene therapy. Curr Opin Immunol 33:112-9 |
| Smith, Sheena N; Harris, Daniel T; Kranz, David M (2015) T Cell Receptor Engineering and Analysis Using the Yeast Display Platform. Methods Mol Biol 1319:95-141 |
| Corrales, Leticia; Glickman, Laura Hix; McWhirter, Sarah M et al. (2015) Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity. Cell Rep 11:1018-30 |
| Gajewski, Thomas F; Corrales, Leticia (2015) New perspectives on type I IFNs in cancer. Cytokine Growth Factor Rev 26:175-8 |
| Spaapen, Robbert M; Leung, Michael Y K; Fuertes, Mercedes B et al. (2014) Therapeutic activity of high-dose intratumoral IFN-? requires direct effect on the tumor vasculature. J Immunol 193:4254-60 |
| Woo, Seng-Ryong; Fuertes, Mercedes B; Corrales, Leticia et al. (2014) STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41:830-42 |
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