Tumor Immunology and Immunotherapy

Program Director:

Michael I. Nishimura, PhD

Members:
Phong Le, PhD
Caroline Le Poole, PhD
Herb Mathews, PhD
Michael Nishimura, PhD
Stephanie Watkins, PhD
Jose Guervara, PhD

 

Phong Le, PhD
Professor
Microbiology & Immunology
ple@luc.edu

 

‌Caroline Le Poole, PhD
Professor
Pathology, Microbiology and Immunology
ilepool@luc.edu

Dr Caroline Le Poole is a full, tenured professor of Pathology and Microbiology& Immunology, and a member of the Oncology Research Institute. She holds a Master’s degree from Utrecht University in Molecular Microbiology, Cell Biology, and Bioprocess Technology and a PhD in Medicine from the Department of Dermatology of the AMC/Amsterdam University in the Netherlands. Dr. Le Poole is the current President of the PanAmerican Society for Pigment Cel Research and Vice President of the International Federation of Pigment Cell Societies.

Research in the Le Poole lab is focused on immunotherapy the etiology and treatment of vitiligo, melanoma and lymphangioleiomyomatosis (LAM) as well as tuberous sclerosis complex (TSC). Specifically, the objective is to design immunotherapeutics to treat these conditions.  This is made possible by the interesting observation that each of these conditions share some common target molecules suitable for treatment by vaccines. In the autoimmune condition vitiligo, the goal is to reduce immune response that affect the livelihood of melanocytes, responsible for generating pigment in the skin. In turn, the immune response that develops in vitiligo patients provides a directive for how to target tumors. Likewise, the understanding that heat shock proteins are overexpressed in tumors in response to hypoxic stress has provided guidelines for a different approach towards autoimmune disease.

Currently ongoing projects in the lab with translational implications include the analysis and cloning of T cell receptors responsible for progressive depigmentation; studies of phenolic compounds that can selectively eliminate pigmented cells; differential expression of ganglioside D3 and immunotherapeutics to target this molecule in TSC; and the use of a modified heat shock protein (HSP70iQ435A) to treat vitiligo and other side effects of immunotherapy in melanoma.

Some publications:

Klarquist J, Eby JM, Henning SW, Li M, Wainwright DA, Westerhof W, Luiten RM, Nishimura MI, Le Poole IC.  Functional cloning of a gp100-reactive T-cell receptor from vitiligo patient skin.  Pigment Cell Melanoma Res. 2016 May;29(3):379-84.

Eby JM, Kang HK, Tully ST, Bindeman WE, Peiffer DS, Chatterjee S, Mehrotra S, Le Poole IC. CCL22 to Activate Treg Migration and Suppress Depigmentation in Vitiligo. J Invest Dermatol. 135:1574-80 (2015)

Bonchak JG, Eby JM, Willenborg KA, Chrobak D, Henning S, Krzywiec A, Johnson SL, Le Poole IC. Targeting melanocyte and melanoma stem cells by 8-hydroxy-2-dipropylaminotetralin. Arch Biochem Biophys, 563:71-8 (2014)

Gilbert ER, Eby JM, Hammer AM, Klarquist J, Christensen DG, Barfuss AJ, Boissy RE, Picken MM, Love RB, Dilling DF, Le Poole IC. Positioning Ganglioside D3 as an Immunotherapeutic Target in Lymphangioleiomyomatosis. Am J Pathol, 2013. 183: 226-34.

Mosenson JA, Zloza A, Nieland JD, Garrett-Mayer E, Eby JM, Huelsmann EJ, Kumar P, Denman C, Lacek AT, Kohlhapp FJ, Alamiri A, Hughes T, Bines SD, Kaufman HL, Overbeck A, Mehrotra S, Hernandez C, Nishimura MI, Guevara-Patino JA, Le Poole IC. Mutant HSP70 reverses autoimmune depigmentation in vitiligo. Science Transl Med 5(174): 174ra28. (2013) 

PHOTO GALLERY
 
Michael I. Nishimura Ph.D
Professor, Department of Surgery
Co-Director, Oncology Institute
Associate Director, Cancer Center Translations Research
Program Director, Immunologic Therapeutics
mnishimura@luc.edu
Office phone: 708-327-3207

Interest: Cancer Immunology and Immunotherapy

My laboratory has had a long standing interest in the genetics of T cell receptor (TCR) genes that mediate recognition of tumor and viral antigens.  In addition to understanding the relationship between the genetics of the TCR and the function of T cells, we have developed the approach of engineering T cells from any patient to express TCR genes isolated for tumor reactive T cell clones.  The resulting TCR gene-modified T cells can recognize tumors in vitro and in vivo.  Therefore, it is now possible to provide any patient with a source of their own T cells capable of targeting their malignancies.

Despite our ability to custom generate tumor reactive T cells for patients, early clinical trials suggest TCR gene modified T cells are not as effective at tumor infiltrating T cells in treating cancer patients.  To improve the therapeutic efficacy of TCR gene modified T cells, my laboratory has several ongoing projects designed to understand the biology of TCR transduced T cells.  Using a combination of mouse in vivo tumor models, in vitro human studies, and clinical trials, my laboratory is studying the mechanisms to increase the persistence and function of adoptively transferred T cells.  We also have mouse and human studies designed to overcome tumor-induced immune suppression.  Another critical problem my laboratory is addressing is how to circumvent tumor immune escape.  And finally, we are developing novel approaches for generating TCR transduced T cells to treat cancer. 


Stephanie Watkins, PhD
Assistant Professor
Department of Surgery
Microbiology & Immunology
swatkins1@luc.edu

Dr. Watkins studied Biology at Bellarmine University in Louisville, KY (2003) and  went on to receive a PhD from the Department of Microbiology and Immunology at the University of Louisville School of Medicine in 2007 for her work on “Therapeutic Targeting of Tumor-Associated Macrophages.”  She continued her studies in tumor immunology as a postdoctoral fellow at the National Cancer Institute in Frederick, MD.  In September 2012, Dr. Watkins was appointed as an Assistant Professor in the Department of Surgery at Loyola University Medical Center, in the Cardinal Bernardin Cancer Center.

Dr. Watkins’ research interest is focused on the regulation of signaling pathways in antigen presenting cells that regulate inflammation and immune suppression. Tumors can escape immune recognition by inhibiting differentiation, maturation, and activation of cells of the immune system. When immune cells infiltrate the tumor, they often become suppressive, further inhibiting an effective anti-tumor immune response.  We recently identified the transcription factor, FOXO3, as a key regulator of dendritic cell (DC)-induced tolerance in murine and human prostate tumors (Watkins et al, JCI, Apr.1, 2011)., FOXO3 was initially reported as a tumor suppressor gene associated with cell cycle regulation but more recently, it was demonstrated to control inflammatory signals and the immunogenicity of DC.  Additionally, our preliminary data suggests there is a gender or hormone bias for FOXO-regulated immune activation. These data imply that while silencing Foxo3 in male patients may lead to productive anti-tumor immunity but, silencing Foxo3 in female patients may have a detrimental effect.  The goal of our work is to identify the mechanisms that regulate the impact of hormone stimulation (androgen and estrogen) on antigen presenting cell development, activation, tumor infiltration and function within the tumor microenvironment.

Jose Guevara-Patino, MD, PhD
Associate Professor
Department of Surgery
jaguevara@luc.edu
 

Our long-term objective as academic scientists is to develop curative T cell-based approaches against cancer. To achieve this goal, the scientific effort of our lab is focused on understanding how memory CD8+ T cells can be generated, maintained, and rescued in tumor-bearing individuals.

The protective immune response against tumors and invading intracellular pathogens relies on the vigorous attack of cytotoxic T lymphocytes (CTLs). Based on these responses, T cell immunotherapy has emerged as one of the most promising approaches for the treatment of malignancies. However, important hurdles have emerged, foremost of which are the physiological state of tolerance or ignorance of the immune system towards self-antigens, tumor-induced suppression (i.e. TGF-β) and T cell exhaustion. Hence, the objective of our lab is to provide a mechanistic basis for how signal cues on T cells can be exploited to overcome these hurdles. We are focusing on the role of the activating NK receptor, NKG2D, on CD8+ T cells in the prevention of T cell suppression by tumor-produced TGF-β and functional exhaustion. Thus, by maintaining their cytolytic function and persistence in tumor-bearing hosts, we will augment anti-tumor CD8 T cell responses. In CD8+ T cells, engagement of the NK receptor, NKG2D, results in augmented T cell receptor (TCR) activation and function, which facilitates recognition and destruction of stressed target cells. Beyond this canonical function, our lab is interested in how NKG2D signaling in CD8+ T cells drives fundamental molecular changes that impact CD8+ T cell function and effector/memory programs. Our goal is to characterize NKG2D signaling biochemically and functionally in relationship with tumor-induced suppression and exhaustion. Altogether, these studies bring important biological and practical information necessary for the design of future immunologically based clinical trials against melanoma and other forms of cancer.