Schoenberger Lab

Schoenberger Lab

"Mainstream cancer treatments such as chemotherapy, radiation and surgery remain important, but there is also strong interest in finding ways to educate the immune system to attack and destroy cancerous cells. New and more effective personalized immunotherapies for cancer will emerge from a clearer understanding of the antigens expressed in a given individual’s tumor and the ability of their own immune system to respond." — Stephen Schoenberger, Ph.D. // Center Head; Professor
Division of Developmental Immunology

Overview

Cancer is a disease of genes, thought to arise in a single cell when those controlling growth and survival progressively sustain function-altering mutations during the process of tumor development. The immune system contains a specialized subset of lymphocytes called T cells, which possess the ability to recognize and kill our own cells when these are found to express foreign genes that signal the presence of a pathogenic virus or bacteria within. Mounting evidence has revealed that this same process which keeps us safe from harmful infections can be used to eradicate cancer by directing T cells to attack the mutations that are exclusively expressed in the tumor cells. Tumor-specific mutations that are recognized by an individual patient’s T cells are called neoantigens, and can form the basis for personalized cancer immunotherapy. Neoantigens can now be readily identified through genomic sequencing and immune responses to them can be generated through vaccination and measured at the level of single cells. Thus, all the tools needed to evaluate and optimize personalized immunotherapeutic approaches to cancer treatment are in place.

My laboratory’s current research is focused on achieving a mechanistic understanding of the generation and regulation of T cell responses in the context of in vivo infection and tumor development. Our work is focused on three main areas. One of these concerns the role of CD4+ ‘helper’ T cells in regulating the response of CD8+ ‘killer’ T cells, where we have found that the degree of inflammation associated with the priming stimulus will determine whether the CD4+ T cell response will help or hinder (regulate) the CD8+ T cells. This work has revealed unexpected roles for CD4+ T cells as well as for specific receptors that sense infectious pathogens, and will help to inform superior vaccination strategies for cancer and infectious disease. A 2nd line of research is directed towards the development of preclinical animal models of cancer immunotherapy, both in the context of adoptive immunotherapy as well as neoantigen-specific cancer vaccines. This work involves identifying the neoantigens expressed in murine and human tumors and optimizing methods for their specific targeting by various targeted vaccines or through adoptive cellular therapy (ACT) with neoantigen-specific T cells. Significant progress has been made in this area through our discovery of a process through which a patient’s tumor cells can be converted to cancer stem cells that retain expression of the neoantigens identified in the original cancer and which can form tumors in immunodeficient mice. Lastly, my laboratory is part of a clinical Head and Neck Cancer immunotherapy Program at UC San Diego’s Moores Cancer Center that is focused on treating patients through neoantigen-specific immunotherapy. Our work in this context is directed towards identifying neoantigens as well as the T cell receptors that recognize them through next-generation sequencing, cellular immunology, and single-cell genomics.

From The Lab

Jul 28, 2016 // La Jolla Light

Frontline Cancer: National Cancer Institute Cancer Centers Council (C3) combine efforts in San Diego

Jul 22, 2015

La Jolla Institute/UCSD team wins CRI CLIP Grant to fund personalized cancer immunotherapy study

Schoenberger Lab

Publications

Sci Transl Med

The human vaccines project: a roadmap for cancer vaccine development

2016-04
Romero P, Banchereau J, Bhardwaj N, Cockett M, Disis ML, Granoff G, Gilboa E, Hammond SA, Hershberg R, Korman AJ,…
Journal of Immunology

CD28 promotes plasma cell survival, sustained antibody responses and BLIMP-1 upregulation through its distal PYAP proline motif

2015-05
Rozanski CH, Utley A, Carlson LM, Farren MR, Murray M, Russell LM, Nair JR, Yang Z, Brady W, Garrett-Sinha LA,…
Nature

Mutant MHC class II epitopes drive therapeutic immune responses to cancer

2015-04
Kreiter S, Vormehr M, van de Roemer N, Diken M, Löwer M, Diekmann J, Boegel S, Schrörs B, Vascotto F, Castle JC,…
Immunology and Cell Biology

FoxO3 is a negative regulator of primary CD8+ T-cell expansion but not of memory formation

2015-02
Togher S, Larange A, Schoenberger SP, Feau S
Nature Medicine

Notch signaling maintains T cell memories

2015-01
Miller AM, Schoenberger SP
Mucosal Immunology

Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells

2015-01
Vicente-Suarez I, Larange A, Reardon C, Matho M, Feau S, Chodaczek G, Park Y, Obata Y, Gold R, Wang-Zhu Y, Lena C,…
Nature Immunology

T cell exhaustion: a means or an end?

2013-06
Salek-Ardakani S, Schoenberger SP
Journal of Immunology

Invariant NKT cells induce plasmacytoid dendritic cell (DC) cross-talk with conventional DCs for efficient memory CD8+ T cell induction

2013-06
Shimizu K, Asakura M, Shinga J, Sato Y, Kitahara S, Hoshino K, Kaisho T, Schoenberger SP, Ezaki T, Fujii S
Journal of Immunology

SLAT regulates CD8+ T cell clonal expansion in a Cdc42- and NFAT1-dependent manner

2013-01
Feau S, Schoenberger SP, Altman A, Bécart S
Nature Communications

The CD4(+) T-cell help signal is transmitted from APC to CD8(+) T-cells via DC27-CD70 interactions

2012-07
Feau S, Garcia Z, Arens R, Yagita H, Borst J, Schoenberger SP
Proceedings of the National Academy of Sciences of the United States of America

CD69 guides CD4+ T cells to the seat of memory

2012-05
Schoenberger SP
Blood

Nab2 regulates secondary CD8+ T-cell responses through control of TRAIL expression

2012-01
Wolkers MC, Gerlach C, Arens R, Janssen EM, Firzgerald P, Schumacher TN, Medema JP, Green DR, Schoenberger SP
Nature Immunology

4th Aegean conference on the crossroads between innate and adaptive immunity

2011-12
Schoenberger SP, Pulendran B, Katsikis PD
Nature Immunology

Mucosal memory CD8(+) T cells are selected in the periphery by an MHC class I molecure

2011-10
Huang Y, Park Y, Wang-Zhu Y, Larange A, Arens R, Bernardo I, Olivares-Villagomez D, Herndler-Brandstetter D, Abraham N,…
Cancer Research

Immune adjuvant efficacy of CpG oligonucleotide in cancer treatment is founded specifically upon TLR9 function in plasmacytoid dendritic cells

2011-10
Nierkens S, den Brok MH, Garcia Z, Togher S, Wagenaars J, Wassink M, Boon L, Ruers TJ, Figdor CG, Schoenberger SP,…
Immunology Letters

Interleukin-2 rescues helpless effector CD8(+) T cells by diminishing the susceptibility to TRAIL mediated death

2011-09
Wolkers MC, Bensinger SJ, Green DR, Schoenberger SP, Janssen EM
Nature Immunology

Autocine IL-2 is required for secondary population expansion of CD8(+) memory T cells

2011-07
Feau S, Arens R, Togher S, Schoenberger SP
Journal of Experimental Medicine

Sustained antibody responses depend on DC28 function in bone marrow-resistent plasma cells

2011-07
Rozanski CH, Arens R, Carlson LM, Nair J, Boise LH, Chanan-Khan AA, Schoenberger SP, Lee KP
Journal of Immunology

B cell-specific expression of b7-2 is required for follicular th cell function in response to vaccinia virus

2011-05
Salek-Ardakani S, Choi YS, Rafii-El-Idrissi Benhnia M, Flynn R, Arens R, Shoenberger S, Crotty S, Croft M,…
Journal of Immunology

Differential B7-CD28 costimulatory requirements for stable and inflationary mouse cytomegalovirus-specific memory CD8 T cell populations

2011-04
Arens R, Loewendorf A, Redeker A, Sierro S, Boon L, Klenerman P, Benedict CA, Schoenberger SP
Immunity

From the loading dock to the boardroom: a new job for Akt kinase

2011-02
Feau S, Schoenberger SP
Journal of Clinical Investigation

The TNFR family members OX40 and CD27 link viral virulence to protective T cell vaccines in mice

2011-01
Salek-Ardakani S, Flynn R, Arens R, Yagita H, Smith GL, Borst J, Schoenberger SP, Croft M
Journal of Virology

B7-mediated costimulation of CD4 T cells constrains cytomegalovirus persistence

2011-01
Arens R, Loewendorf A, Her MJ, Schneider-Ohrum K, Shellam GR, Janssen E, Ware CF, Schoenberger SP, Benedict CA
PLoS One

Polyfunctional CD4(+) T cell responses to immunodominant epitopes correlate with disease activity of virulent salmonella

2016-08
Maybeno M, Redeker A, Welten SP, Peters B, Loughhead SM, Schoenberger SP, Sette A, Arens R

Principal Investigator

schoenberger

Stephen Schoenberger, Ph.D.

Center Head; Professor

Dr. Schoenberger joined LIAI in 1998 as an Assistant Professor in the Division of Immune Regulation. In 2002, Dr. Schoenberger became an Associate Professor in the Division of Cellular Immunology, and in 2005 gained Tenure. In 2008, he was promoted to Professor. Dr. Schoenberger’s research focuses on the regulation of cellular immune responses.

Dr. Schoenberger received his B.S. from the University of California, Los Angeles in 1987 and his Ph.D. from the same university in 1992. In 1993, Dr. Schoenberger was a Postdoctoral Fellow in Immunohematology at the University of Leiden Hospital, the Netherlands, from 1993-1998.

Dr. Schoenberger is a member of numerous grant review panels and a reviewer for many scientific publications. He is also a member of the editorial advisory board for the Journal of Experimental Medicine.

Lab Members

Milad Bahmanof

Research Technician II

Claire Chen

Intern

Ana Chiodetti

Graduate Student

Ariel Chou

Intern

Joseph Dolina, Ph.D.

Postdoctoral Fellow

Biosketch:
In 2006, Joseph obtained B.S. degrees in Biology and Chemistry from The College of New Jersey. This was shortly followed by a M.S. in Biomedical Sciences in 2007 from the University of Medicine and Dentistry of New Jersey. From 2007-2013 Joseph completed his doctoral work at the University of Virginia obtaining his M.S. and Ph.D. in Microbiology. Dr. Dolina then joined the La Jolla Institute as a postdoctoral fellow in 2014 in the Schoenberger laboratory.

Research Focus:
The long term aim of my research is to understand the molecular and cellular signals that program an antigen-specific CD8+ CTL-based immune response against infection or cancer. I focus my research on determining the nature of CD4+ T cell help: namely how inflammation alters the Teff:Treg balance and subsequent CD8+ CTL response, in which contexts the CD8+ CTL responses is rendered help-dependent or help-independent, when IL-2 is needed by CTLs in autocrine or paracrine, and determining the antigen presenting cell type that specifically receives the CD40/CD40L signal and relays CD27/CD70-mediated help.

Career Goals:
I plan to pursue a career in academia or pharmaceutical research on projects where T cells are the focus. I have and will continue to aim my professional career at understanding how these cells work and how the power of these cells can be harnessed to treat relevant diseases.

Doug Ethell

Visiting Scientist

Ariel Floro

Intern

Yongchul Kim

Postdoctoral Fellow

Yvonne Kwan

Intern

Joey Lee

Research Technician I

Yun-Jung Lee

Postdoctoral Fellow

Aaron Miller, MD, PhD

Clinical Fellow

Leslie Montero, M.D.

Research Associate

Maulik Patel

Visiting Scientist

Catherine Waczek

Laboratory Assistant

Jessica Xiao

Research Technician

Sharon Xu

Laboratory Assistant

Schoenberger Lab

Research Projects

Dr. Schoenberger is a Professor in the Laboratory of Cellular Immunology and Chair of LIAI’s Center for the Immunobiology of Cancer, as well as an Adjunct Professor of Medicine in the Division of Hematology and Oncology at the UCSD Moores Cancer Center. He received his Ph.D. in Microbiology and Molecular Genetics from UCLA in 1993 and completed postdoctoral training in Immunohematology and Tumor Immunology at the University of Leiden in The Netherlands. Dr. Schoenberger was appointed to LIAI’s faculty in 1998 as an Assistant Professor, became an Associate Professor in 2002, gained Tenure in 2005, and became a Professor in 2007. He is a recipient of Scholar Awards from both the American Cancer Society and the Leukemia and Lymphoma Society, and is on the editorial advisory board of the Journal of Experimental Medicine.

Dr. Schoenberger is a leader in the immunobiology of CD4+ and CD8+ T cell responses with particular expertise on the generation and maintenance of immune memory by these subsets and in the key role of antigen-presenting cells (APC) in mediating antigen-specific tolerance versus immunity. His research has revealed a new mechanism for how CD4+ T cells provide the ‘help’ necessary for optimal CD8+ T cell responses via APC activation and his laboratory was the first to demonstrate the role of T cell programming in guiding the development of CD8+ T cells. More recently, he has sought to translate his laboratory’s insights into T cell and APC biology for the personalized immunotherapy of cancer based on patient-specific tumor neoantigens in work that will lead to clinical trials at the Moores Cancer Center planned for later in 2016.