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Hans Schreiber, M.D., Ph.D.
Tumor Immunology; Tumor Progression, Tumor-Specific
T-cell Clones; Characterization of Tumor Variants; Molecular Genetics
of Tumor Antigens
Research Summary
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.
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