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. // Professor


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

Apr 7, 2020 // Cell Reports

Too Much Haste Leads to Little Speed

A Newly Discovered Biological Switch Evolved to Stimulate the Immune System can also Lead to Immune Paralysis
Sep 3, 2019 // UT San Diego

UCSD’s cancer vaccine trial shows range of results at the one-year mark

Oct 18, 2018

La Jolla Institute receives $ 4.5 mill Cancer Moonshot award

The grant will help improve existing immunotherapeutic options; accelerate the development of novel cancer vaccines and personalized therapies for the treatment of head and neck cancer
Oct 12, 2018

Is the Next Big Step in Cancer Therapy: Personalized Vaccines?

UC San Diego Health and La Jolla Institute launch clinical trial harnessing an individual’s immune system in a syringe
Sep 4, 2018

Turnstone Biologics and the La Jolla Institute for Immunology Enter into Strategic Collaboration for Personalized Neoantigen Immunotherapies

Turnstone Obtaining License to Neoantigen Identification Methodology Developed by the La Jolla Institute

Schoenberger Lab


J Leukoc Biol

Harnessing Neoantigen Specific CD4 T Cells for Cancer Immunotherapy

Brightman SE, Naradikian MS, Miller AM, Schoenberger SP.
Cancer Immunol Res

Irreversible electroporation combined with checkpoint blockade and TLR7 stimulation induces antitumor immunity in a murine pancreatic cancer model

Narayanan JSS, Ray P, Hayashi T, Whisenant TC, Vicente D, Carson DA, Miller AM, Schoenberger SP, White RR
Front Immunol

A threshold model for T-cell activation in the era of checkpoint blockade immunotherapy

Guram K, Kim SS, Wu V, Sanders PD, Patel S, Schoenberger SP, Cohen EEW, Chen SY, Sharabi AB
Cancer Immunol Res

Leveraging TCR affinity in adoptive immunotherapy against shared tumor/self-antigens

Miller AM, Bahmanof M, Zehn D, Cohen EEW, Schoenberger SP
Cold Spring Harb Perspect Biol

Is it possible to develop cancer vaccines to neoantigens, what are the major challenges, and how can these be overcome? Targeting the right antigens in the right patients

Schoenberger SP
Front Immunol

Class-B CpG-ODN formulated with a nanostructure induces type I interferons-dependent and CD4+ T cell-independent CD8+ T-cell response against unconjugated protein antigen

Chiodetti AL, Sánchez Vallecillo MF, Dolina JS, Crespo MI, Marin C, Schoenberger SP, Allemandi DA, Palma SD,…
J Transl Med

Perspectives in melanoma: Meeting report from the melanoma bridge (30 November-2 December, 2017, Naples, Italy)

Ascierto PA, Puzanov I, Agarwala SS, Bifulco C, Botti G, Caracò C, Ciliberto G, Davies MA, Dummer R, Ferrone S,…
J Transl Med

Perspectives in melanoma: Meeting report from the melanoma bridge (30 November–2 December, 2017, Naples, Italy)

Ascierto PA, Puzanov I, Agarwala SS, Bifulco C, Botti G, Caracò C, Ciliberto G, Davies MA, Dummer R, Ferrone S,…
J Clin Invest

T cells control the generation of nanomolar-affinity anti-glycan antibodies

Polonskaya Z, Deng S, Sarkar A, Kain L, Comellas-Aragones M, McKay CS, Kaczanowska K, Holt M, McBride R, Palomo V, Self…
Sci Transl Med

The human vaccines project: a roadmap for cancer vaccine development

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

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

Mutant MHC class II epitopes drive therapeutic immune responses to cancer

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

Togher S, Larange A, Schoenberger SP, Feau S
Nature Medicine

Notch signaling maintains T cell memories

Miller AM, Schoenberger SP
Mucosal Immunology

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

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?

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

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

Feau S, Schoenberger SP, Altman A, Bécart S
PLoS One

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

Maybeno M, Redeker A, Welten SP, Peters B, Loughhead SM, Schoenberger SP, Sette A, Arens R
Nature Communications

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

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

Schoenberger SP

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

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

Schoenberger SP, Pulendran B, Katsikis PD
Nature Immunology

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

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

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

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

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

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

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

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

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

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

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

Arens R, Loewendorf A, Her MJ, Schneider-Ohrum K, Shellam GR, Janssen E, Ware CF, Schoenberger SP, Benedict CA
J Leukoc Biol

TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion

Gurung P, Kucaba TA, Schoenberger SP, Ferguson TA, Griffith TS
Eur J Immunol

Enhancement of proliferation and downregulation of TRAIL expression on CD8+ T cells by IL-21

Melief CJ, Schoenberger SP
Immunol Cell Biol

Distinct Roles of cytolytic effector molecules for antigen-restricted killing by CTL in vivo

Janssen EM, Lemmens EE, Gour N, Reboulet RA, Green DR, Schoenberger SP, Pinkoski MJ
J Immunol

Separate roles for antigen recognition and lymph node inflammation in CD8+ memory T cell formation

Fransen MF, Van Stipdonk MJ, Slutijter M, Schoenberger SP, Melief CJ, Offringa R
Adv Exp Med Biol

Memory T Cells. Preface

Zanetti M, Schoenberger SP
Immunol Rev

Plasticity in programming of effector and memory CD8 T-cell formation

Arens R, Schoenberger SP
Nat Immunol

The 2010 Midwinter Conference of Immunologists at Asilomar

Schoenberger SP, Cheroutre H, Uittenbogaart C, Marshak-Rothstein A
Nat Immunol

Effectors and memories: Bcl-6 and Blimp-1 in t and B lyphocyte differentiation

Crotty S, Johnston RJ, Schoenberger SP

Principal Investigator

Stephen Schoenberger, Ph.D.


Dr. Schoenberger joined LIAI in 1998 as an Assistant Professor. In 2002, Dr. Schoenberger became an Associate Professor, 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

Cheryl Andreoli

Visiting Scientist

Milad Bahmanof

Research Technician II

I graduated from University of California – San Diego with a degree in Biochemistry and Cell Biology. After becoming passionate about immunology, I joined Dr. Schoenberger’s lab to continue learning about the immune system, specifically focusing on T cells.

Research Focus:
I work on exome-guided cancer neo-antigen discovery. With the information gained, I establish patient-derived xenograft models and identify their reactive tumor infiltrating lymphocytes. I am also involved with creating a model for on-target and off-target toxicity observed in many cancer therapies, which lead to autoimmunity.

Career Goals:
I plan to pursue a medical degree and focus my research on translational medicine. I hope, as a future physician, that I can provide for underserved communities, locally and internationally.

Angelica Becker

Lab Assistant

Spencer Brightman

Graduate Student

Sarina Chadha

Intern (non-paid)

Elaine Eng


Ryan Griswold

Graduate Student

Malak Jaljuli


Jessica Jou

Visiting Scientist

Aaron Miller, MD, PhD

Clinical Associate

Aaron M. Miller, MD, PhD, is a board-certified medical oncologist who specializes in diagnosing and treating gastrointestinal cancers. This includes cancers of the esophagus, gallbladder, liver, pancreas, stomach, small intestine, bowel and anus. He uses numerous forms of therapy such as chemotherapy, biological therapy, immunotherapy and targeted therapy to offer the best possible treatment options for his patients. Dr. Miller’s approach to care emphasizes personalized medicine/precision oncology, adoptive cellular therapy, next-generation tumor sequencing and tumor immunology. He is part of the gastrointestinal cancer unit at Moores Cancer Center at UC San Diego Health, where he works alongside a multidisciplinary team to provide patients with highly specialized care.

Dr. Miller is an assistant professor in the Department of Medicine, where he instructs medical students, residents and fellows at UC San Diego School of Medicine. He holds a joint faculty appointment at the La Jolla Institute for Immunology and is actively involved in cancer research, with the aim of translating his discoveries in the lab into new ways of treating patients.

Specifically, Dr. Miller’s research focuses on tumor neoantigen identification as targets for novel immunotherapeutics that are both effective and avoid off-tumor toxicities. He and his colleagues have also created a new patient-derived xenograft platform that allows for preclinical testing of investigational chemotherapeutics and immune therapies.

He has co-authored several peer-reviewed articles and his work has appeared in Nature Medicine and Advanced Drug Delivery Reviews, among others.

Dr. Miller completed a fellowship in hematology-oncology at UC San Diego School of Medicine, where he also completed a residency in internal medicine. He earned his medical degree from the Feinberg School of Medicine and a doctoral degree from the Graduate School, both at Northwestern University. Dr. Miller is board-certified in internal medicine and medical oncology.

He is a member of numerous professional organizations, including the American Society of Clinical Oncology, the American Association for Cancer Research and the American Medical Association.

Leslie Montero, M.D.

Research Associate

Thi Nguyen

Intern (non-paid)

Rukman Thota


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.