Research Program: Immunology
Director, University of Minnesota Center for Immunology
Professor, Department of Laboratory Medicine and Pathology
Virginia and David C. Utz Land Grant Chair in Fundamental Immunobiology

mesch001@umn.edu
612-626-2368 — office
612-612-626-2476 — lab
Preferred contact method: e-mail

Dr. Mescher received his Ph.D. in biochemistry and molecular biology in 1976 from Harvard University. He then joined the faculty of the Department of Pathology at Harvard Medical School as an assistant professor and then associate professor. In 1985 he moved to the Medical Biology Institute in La Jolla, Calif., to become chief of the Division of Membrane Biology. He became a professor in the Department of Laboratory Medicine and Pathology at the University of Minnesota in 1993, and was appointed the director of the Center for Immunology when it was formed in 1995.

Research Interests

Cytotoxic T lymphocytes (CTL), also known as "killer cells", are CD8 T lymphocytes that play an important role in immune defense by directly binding to and killing tumor or virus-infected cells. Dr. Mescher's laboratory studies the requirements for effective activation of these cells using both in vitro and in vivo approaches. These studies employ, in part, novel methods for producing artificial membrane constructs using purified membrane proteins including class I MHC antigens and costimulatory ligands. This provides a means for precisely defining the molecular interactions and signaling pathways required for effective activation of the CD8 T cells. This approach has recently led to the discovery that signals delivered by specific inflammatory cytokines (IL-12, IFN-alpha/beta) are required to stimulate differentiation of the CD8 T cells to develop effector functions and become active "killer cells". Ongoing studies are analyzing the signaling pathways and molecular mechanisms involved in regulation of gene expression by these cytokines. In other work in the laboratory, as new aspects of the requirements for CD8 T cell activation are found, these are applied to the development of novel approaches for tumor immunotherapy that target activation of tumor specific CTL. A number of different murine tumor models are used to evaluate these approaches for their effects on CD8 T cell activation in the tumor-bearing mouse, and the resulting effects on tumor growth and host survival. One such approach that demonstrated efficacy in several murine tumor models is currently in being tested in clinical trials for treatment of melanoma and renal carcinoma, in collaboration with clinical researchers in the Masonic Cancer Center.

Selected Publications

Mitchell MS, Kan-Mitchell J, Morrow PR, Darrah D, Jones VE, Mescher MF. Phase I trial of large multivalent immunogen (LMI) derived from melanoma lysatesin patients with disseminated melanoma. Clin Cancer Res. 2004;10:76-83.

Valenzuela J, Hammerbeck C, Mesche rMF. Cutting Edge: Bcl-3 upregulation by signal 3 cytokine (IL-12) prolongs survival of Ag-activated CD8 T cells. J Immunol. 2005;174:600-604.

Curtsinger JM, Valenzuela JO, Agarwal P, Lins D, Mescher MF. Cutting Edge: Type I interferons provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J Immunol. 2005;174:4465-4469.

Mescher MF, Curtsinger JM, Agarwal P, Casey KA, Gerner M, Hammerbeck CD, Popescu F, Xiao, Z. Signals required for programming effector and memory development by CD8 T cells. Immunol Rev. 2006;Jun;211:81-92.

Curtsinger JM, Gerner MY, Lins DC, Mescher MF. Signal 3 availability limits the CD8 T cell response to a solid tumor. J Immunol. 2007;178:6752-6760.

Mescher MF, Agarwal P, Casey KA, Hammerbeck CD, Xiao Z, Curtsinger JM. Molecular basis for checkpoints in the CD8 T cell response: Tolerance versus full activation. Sem Immunol. 2007;19:153-161.

Casey KA,Mescher MF. IL-21 promotes differentiation of naïve CD8 T cells to a unique effector phenotype. J Immunol. 2007;178:7640-7648.

Xiao Z, Mescher MF, Jameson SC. Detuning CD8 T cells: Down-regulation of CD8 expression, tetramer binding and response during CTL activation. J Exp Med. 2007;204:2667-2677.

Hammerbeck CD, Mescher MF. Antigen regulates IL-7Ralpha expression levels on CD8 T cells during full activation or tolerance induction. J Immunol. 2008;180:2107-2116.

Dudek, A.Z., M.F. Mescher, I. Okazaki, V.T. Math, X. Luo, J.M. Curtsinger and J.S. Miller. Autologous large multivalent immunogen vaccine (LMI) in patients with metastatic melanoma and renal cell carcinoma. Am. J. Clin. Oncol. 31:173-181 (2008).

Gerner, M.Y., K.A. Casey and M.F. Mescher. Defective MHC-II presentation by DC limits CD4 T cell help for anti-tumor CD8 T cell responses. J. Immunol. 181:155-164 (2008).

Xiao, Z., K.A. Casey, S.C. Jameson, J.M. Curtsinger and M.F. Mescher. Programming for CD8 T cell memory requires IL-12 or Type I IFN. J. Immunol. 182:2786-2794 (2009).

Gerner, M.Y. and M.F.Mescher. Antigen processing and MHC-II presentation by dermal and tumor infiltrating dendritic cells. J. Immunol. 182:2726-2737 (2009).