The main focus of this laboratory is to study the fundamental mechanisms that govern the interaction of cancer cells with the immune system. In particular, our laboratory is trying to exploit the fact that cancer cells usually carry cancer-specific mutations and antigens, and that, under certain conditions, the immune system can destroy cancer cells even after they have disseminated in the body. We are trying to understand the mechanisms that often allow immunogenic cancer cells to escape immune destruction, and we want to develop new strategies and principles on which to base novel therapeutic approaches. We are also studying the signals needed for the immune system to be alerted by cancer cells, and then to destroy these cells. For these studies we are using newest molecular tools and novel bio-engineered molecules and technologies. Finally, we combine immunology with genetics and biochemistry, a combination that provides a most powerful tool to search for cancer-specific changes in malignant cells. Identification of these changes may not only identify critical causative mechanisms but also new immunological and pharmacological targets that can be used to destroy the cancer.

Some of the ongoing projects in my laboratory are:

1. Mechanism of tumor escape from host immunity. Development of new strategies to prevent this escape by genetic engineering and immune manipulations.

2. Mechanisms leading to paracrine stimulation of tumor growth. Novel
approaches of using tumor stroma as therapeutic target.

3. Use of tumor-specific mutant proteins or viral oncoproteins (E6/E7 of HPV) as target for immune prevention of primary cancer development.

4. Identification of the molecular basis and genetic origins of tumor-specific target antigens and target molecules that cannot be lost by cancer cells.

Selected Papers

Beck, C., K. Schreiber, H. Schreiber, and D.A. Rowley. ckit+ FcR+ myelocytes are increased in cancer and prevent the proliferation of fully cytolytic T cells in the presence of immune serum. Eur. J. Immunol. 33:19-28, 2003.

Yu, P., M.T. Spiotto, H. Schreiber, and Y. Fu. Complementary role of CD4+ T cells and secondary lymphoid tissues for cross-presentation of tumor antigens to CD8+ T cells. J. Exp. Med. 197:985-95, 2003.

Spiotto, M.T., M. Reth, and H. Schreiber. Genetic changes occurring in established tumors rapidly stimlate new antibody responses. Proc. Natl. Acad. Sci. USA,100:5425-30, 2003.

Schreiber, H. Tumor Immunology. Chapter 48. In: Fundamental Immunology 5th edition. W.E. Paul, ed. Lippincott Raven Press, New York pp 1557-1592, 2003.

Yu, P. Spiotto, M.T., Lee Y, Schreiber, H. and Fu, Y.X . Complementary role of CD4+ T cells and secondary lymphoid tissues for cross-presentation of tumor antigens to CD8+ T cells. J. Exp. Med. 197:985-95, 2003.

Spiotto, M., Reth, M. and Schreiber, H. Genetic changes occurring in established tumors rapidly stimulate new antibody responses. Proc. Natl. Acad. Sci. USA,100:5425-30, 2003.

Spiotto MT, Fu YX, Schreiber H. Tumor immunity meets autoimmunity: antigen levels and dendritic cell maturation. Curr Opin Immunol. 15:725-30, 2003.

Wu TH, Pabin CN, Qin Z, Blankenstein, T, Philip M, Dignam J, Schreiber K, and Schreiber H. Long-term suppression of tumor growth by TNF requires a Stat1- and IRF-1-dependent IFNγ pathway but not IL-1 or IL-18. J. Immunol. 172: 3243-51, 2004.

Yu P, Lee Y, Liu W, Chin RK, Wang J, Wang Y, Schietinger A, Philip M, Schreiber H, Fu YX. Priming of naive T cells inside tumors leads to eradication of established tumors. Nature Immunology 5: 141-9, 2004.

Spiotto MT, Rowley DA, and Schreiber H “Bystander” elimination of antigen loss variants in established tumors. Nature Medicine 10: 294-8, 2004.

Schreiber K, Cannon RE, Karrison T, Beck-Engeser G, Huo D, Tennant RW, Jensen H, Kast WM, Krausz T, Meredith SC, Chen L, and Schreiber H. Strong synergy between mutant ras and HPV16 E6/E7 in the development of primary tumors. Oncogene, 23:3972-9, 2004.

Philip, M., Rowley, D.A., and Schreiber, H. Inflammation as a tumor promoter in cancer induction. Sem. Cancer Biol. 14:433-439, 2004.

Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber, H, and Fu YX. Intra-tumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J. Exp. Med. 201: 779-791, 2005.

Spiotto MT, and Schreiber H. Rapid destruction of the tumor microenvironment by CTLs recognizing cancer-specific antigens cross-presented by stromal cells.. Cancer Immun. 5:8 (7 pages) 2005.

Yu P, Rowley DA, Fu YX, Schreiber H. The role of stroma in immune recognition and destruction of well-established solid tumors. Curr. Opin. Immunol. 18: 226-231, 2006.

Schreiber K, Rowley DA, Riethmuller G, Schreiber H. Cancer immunotherapy and preclinical studies: why we are not wasting our time with animal experiments. Hematol Oncol Clin North Am. 20:567-84, 2006.

Spiotto MT and Schreiber H. Floxed Reporter Genes: Flo High Level of a Target Gene after Tamoxifen-Regulated CreloxP Recombination. J. Immunol. Meth. 312:201-8, 2006.

Schietinger A, Philip M, Yoshida BA, Azadi P, Liu H, Meredith SC, Schreiber H. A mutant chaperone converts a wild-type protein into a tumor-specific antigen. Science. 314:304-8, 2006.

Zhang B., Bowerman N., Salama J, Schmidt H, Spiotto MT, Rowley DA, Schietinger A, Yu P, Fu YX, Weichselbaum RR, Kranz DM, and Hans Schreiber H. Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. J. Exp. Med. 204:49-55, 2007.

Gabrilovich DI, Bronte V, Chen SH, Colombo MP, Ochoa A, Ostrand-Rosenberg S, and Schreiber H. The terminology issue for myeloid-derived suppressor cells. Cancer Res.67:425, 2007.

Yu P, Lee Y, Wang Y, Christiansen P, Liu X, Gajewski TF, Schreiber H, Wang X, and Fu Y-X. Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastasis, J. Immunol. 179:1960-8, 2007.

Schreiber H, and Rowley DA. Cancer. Quo vadis, specificity? Science. 319:164-5. 2008.

Zhang, B, Karrison T, Rowley,DA and Schreiber H. IFN-g- and TNF-dependent bystander eradication of antigen-loss variants in established mouse cancers. J. Clin. Invest. 118:1398-404. 2008.

Zhang, B, Zhang Y, Bowerman N, Rowley DA, Schietinger A, Schietinger A, Fu YX, Kranz DM, Rowley,DA, and Schreiber H. Equilibrium between host and cancer caused by T cells killing tumor stroma. Cancer Res. 68:1563-71, 2008.

Schietinger A, Philip M, Schreiber H. Specificity in cancer immunotherapy. Semin Immunol. 2008 Aug 4.

Faculty and Research

Programs

Cancer Biology

Immunology

Microbiology

Molecular Metabolism
and Nutrition

Molecular Pathogenesis and
Molecular Medicine