Cancer Immunology

Faculty active in this area of research are listed below. For a brief description of their research interests, click on their name in the list. Clicking on the name at the beginning of the brief description links to their detailed personal website.

Donald J. Buchsbaum, PhD, Department of Radiation Oncology
Jessy Deshane, PhD, Department of Medicine
Craig Elmets, MD, Department of Dermatology
Vithal K. Ghanta, PhD, Department of Biology
G. Yancey Gillespie, PhD, Department of Surgery
Judith A. Kapp, PhD, Department of Ophthalmology
Christopher Klug, PhD, Department of Microbiology
Lawrence S. Lamb, Jr., PhD, Department of Medicine
Robin G. Lorenz, MD, PhD, Department of Pathology
Joseph Murphy, PhD, Southern Research Institute
Laura Timares, PhD, Department of Dermatology
Nabiha Yusuf, PhD, Department of Dermatology



Donald J. Buchsbaum, PhD Dr. Buchsbaum’s research is focused on the use of agonistic monoclonal antibodies that bind to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors for cancer therapy in combination with chemotherapy agents or radiation. The research involves investigation of the mechanisms of enhanced cytotoxicity produced by combination treatment with TRAIL death receptor antibodies and chemotherapy or radiation therapy. Orthotopic and metastatic breast, ovarian, and pancreatic cancer xenograft models are being used to optimize therapeutic regimens. In collaboration with investigators from the Divisions of Gynecologic Oncology and Clinical Immunology, surgical specimens from patients with ovarian cancer are being utilized to develop a tumor slice assay to attempt to correlate in vitro cytotoxicity sensitivity to treatment with death receptor antibody and chemotherapy to patient survival following treatment with humanized antibody and taxol/carboplatin. If successful, this could be used as a predictive assay to select patients for treatment. We are also investigating the use of small molecule modulators of apoptosis to increase the level of tumor cell killing. Other research involves investigating the mechanism by which basal-like triple negative breast cancers are sensitive to death receptor antibody treatment, and the response of basal-type breast cancer stem cells to treatment with TRAIL receptor antibodies, gamma secretase inhibitors, and chemotherapy.


Jessy Deshane, PhD
 Dr. Deshane is committed to an academic career combining basic and translational research with an emphasis on inflammatory diseases of the airway. The focus of Dr. Deshane's research program is to enhance our understanding of the role of myeloid-derived regulatory cells in chronic airway inflammatory diseases. Asthma is a chronic inflammatory disease of the airways in which innate and adaptive immune cells participate as drivers of the inflammatory response. Free radical species have long been implicated as critical mediators of the asthmatic inflammatory process. Dr. Deshane's studies in a mouse model of allergic airway inflammation have established that subsets of free radical-producing myeloid-derived regulatory cells (MDRC) are master regulators of airway inflammation. They are potent modulators of both T cell responses and airway hyper-responsiveness. Dr. Deshane has identified human MDRC with similar function in bronchoalveolar lavage of asthmatics. Her current research interests are (1) to explore the free radical and cytokine/chemokine mediated mechanisms underlying the differentiation and function of myeloid derived regulatory cells in the establishment of airway inflammation and resolution of inflammation (2) to investigate MDRC- mediated regulation of the balance of Tregulatory cells and Th17 cells which control the tolerance vs inflammation (3) to understand how environmental pollutants such as tobacco smoke would impact MDRC function and contribute to exacerbation of inflammation in asthmatic smokers. These studies will provide insight into the role of MDRC in tobacco related pathology of the lung.


Craig A. Elmets, MD Dr. Elmets’ research focuses on the interaction of environmental agents with the skin. His research has particular relevance to skin cancer and cutaneous allergic reactions. In the area of skin cancer, his interests are on skin cancer chemoprevention and therapy. He has played a key role in defining the mechanisms by which the immune system controls the development of skin cancers. More recent studies have centered on the identification of new agents that can protect against skin cancer and on the non-surgical treatment of these malignancies. These include the arthritis drug celecoxib and extracts of green tea. He has also played a major role in the development of photodynamic therapy as a treatment for cancer. Photodynamic therapy utilizes light activated drugs to eradicate cancer. Dr. Elmets’ other area of research is on allergic contact dermatitis, of which poison ivy is the best-known example. He is evaluating better and more accurate diagnostic techniques for contact allergies. His studies have shown that certain proteins called cytokines are synthesized in skin cells from allergic individuals exposed to contact allergens but not in those obtained from people who are the not allergic. These findings provide the conceptual framework for the development of a diagnostic test for skin allergy testing, which can used by physicians and by industry as an alternative to animal testing prior to the introduction of new products into the marketplace.


Vithal K. Ghanta, PhD The research interests of our group are the treatment of cancer at multiple modality levels, quantitation of tumor load, follow-up of the response of tumors to different agents and modalities, understanding the interactions between the immune and central nervous systems, and the changes that take place in the immune system with age. I am interested in developing new approaches for the treatment of cancer, including combination treatments like passive therapy, immune stimulation, and chemotherapy. Secondly, our group has developed a conditioning paradigm for an increase in natural killer cell and cytotoxic T-lymphocyte activities. The model is used extensively in our laboratory to study the mechanisms of central nervous and the immune system interactions and the mechanisms of conditioned regulation of tumor growth.


G. Yancey Gillespie, PhD The main thrust of Dr. Gillespie's research is to develop and test specific therapies for treatment of malignant brain tumors in adults and children. One current focus is construction of replication conditional herpes simplex viruses that are both oncolytic for glioma cells and express foreign therapeutic genes. Gene transfer includes both pro-drug converting enzymes and cytokines under different promoter systems. Pro-drug enzyme systems currently being studied are cytosine deaminase (CD) alone or as a fusion protein with uracil phosphoribosyl transferase (UPRT) and purine nucleoside phosphorylase (PNP). A second focus involves studies with the CD and CDUPRT systems in both replication incompetent adenovirus and conditionally replication competent adenovirus. Adenoviruses targeted to cell surface receptors on glioma cells are being constructed to provide tumor specificity. Cytokines expressed from replication competent HSV that are being studied include TNFa, IL-2, IL-4, IL-5, IL-10, IL12, IL-16. These systems are validated by in vitro assays first before being advanced to safety and efficacy assessment in a variety of murine models of intracranial malignant gliomas. These models include transplantable intracranial gliomas of human origin (in immunocompromised scid or nude mice) or mouse origin (in syngeneic conventional mice). Dr. Gillespie's group also has acquired 2 transgenic glioma mouse models and use high-field strength (8.5T) magnetic resonance imaging to detect and monitor tumor growth in transgenic mice. One intriguing observation is the fact that many of these viral oncolytic and transgene therapies are markedly enhanced by modest doses of whole brain irradiation. This phenomenon is being studied at the cellular and molecular levels to determine how it can be best employed as a therapeutic strategy. Vectors that are to be advanced to clinical trials are tested for neurotoxicity in non-human primates. Finally, small peptides that exert an anti-angiogenic effect on tumor neovasculature or that induce apoptosis in human glioma cells are being studied as therapeutic agents in vitro and in animal models of malignant brain tumors.


Judith A. Kapp, PhD Dr. Kapp's research focuses on identifying mechanisms of inducing and abrogating immunological tolerance. Our long-term goal is to translate our findings into novel therapies for preventing graft rejection and augmenting tumor immunity.

Dr. Kapp's ongoing, studies are directed to basic and clinical aspects of immune regulation by T cells. We have recently focused on the regulatory role of γδ T cells in tolerance. Depletion of γδ T cells prevents tolerance as measured by antibody, CD4+, and CD8+ effector T cell responses induced by oral administration of antigen (Ke, Y., K. Pearce, J. P. Lake, K. Ziegler, and J.A. Kapp. J. Immunol. 158:3610-3618, 1997). To determine whether intraepithelial γδ T cells in the small intestine play a role in oral tolerance, her group has cloned them and found that they are highly immunosuppressive (Kapp, J.A., L.M. Kapp, K.C. McKenna, and J.P. Lake. Submitted). These observations suggested that γδ T cells play a critical, active role in tolerance induced by orally administered antigen. Their studies also show that the immunoregulatory role of γδ T cells is not limited to oral tolerance but extends to systemic tolerance induced by delivery of antigen into the anterior chamber of the eye (Xu, Y. and J.A. Kapp. Immunol. 104:142-148, 2001; Xu, Y. and J.A. Kapp. Invest. Opthalmol. Vis. Sci. 43:3473-3479, 2002), an immunologically privileged site.

Dr. Kapp and colleagues are interested in whether γδ T cells might also play a role in the failure of the immune system to control tumor growth in spite of the fact that many tumors express specific antigens. The failure of tumors to stimulate effective immune responses has been attributed, in part, to their lack of co-stimulatory molecules. Tumors lacking co-stimulatory molecules may induce tolerance rather than immunity leading to progressive tumor growth. As a model system, we used the ovalbumin (OVA) transfected EL4 tumor, called E.G7-OVA, which grows progressively in syngeneic mice even though it can be rejected if the mice are immunized with OVA in adjuvant. E.G7-OVA grew more rapidly in immunodeficient Rag-1 knockout mice than in immunocompetent mice suggesting that normal mice make an abortive immune response to this tumor. Depletion of γδ T cells augmented the ability of mice to reject E.G7-OVA. Moreover, spleen cells from normal, but not IL-10 knockout, mice reconstituted rapid tumor growth in γδ T cell-deficient mice. Thus, we conclude that γδ T cells play an important role in preventing immune elimination of this tumor by a mechanism that directly or indirectly involves IL-10 (Ke, Y., L.M. Kapp, and J.A. Kapp. Cell. Immunol. 221:107-114, 2003).

To test whether E.G7-OVA induced tumor-specific tolerance in the presence of normal γδ T cells, the group used drug therapy to ablate the tumors before testing for tolerance. The alkaloid, noscapine, was used because it has been determined to be a novel anti-mitotic drug that induces tumor regression (Ye, K., Y. Ke, N. Keshava, J. Shanks, J.A. Kapp, R.R. Tekmal, J. Petros, and H.C. Joshi. Proc. Nat. Acad. Sci. 95:1601-1606, 1998). Noscapine, given parenterally or in the drinking water, induces apoptosis of E.G7-OVA and causes regression of this tumor without adverse effects on normal tissues or inhibition of immune responses (Ke, Y., K. Ye, H.E. Grossniklaus, D.R. Archer, H.C. Joshi, and J.A. Kapp. Cancer Immunol. Immunother. 49: 217-225, 2000). These results form the basis of a Provisional Patent Application (No. 60/057,037).

The majority of tumors in the mice that received noscapine disappeared and did not return during continuous treatment with the drug. After four months, the surviving mice and untreated control B6 mice were injected with OVA in adjuvant to test whether the tumor had induced tolerance to OVA. The noscapine treated mice developed OVA antibody and CD4+ T cell responses equivalent to normal mice but OVA-specific CD8+ CTL responses that were 10- to 30-fold greater than the responses of controls. Although these results do not allow determination of whether the tumor induced tolerance in the absence of noscapine, they raise the interesting possibility that noscapine may have potent adjuvant activity for CTL in addition to its anti-mitotic effects. Dr. Kapp is particularly interested in testing the efficacy of noscapine in the treatment of other types of tumors. In addition, her group is investigating the possibility that its adjuvant effects may promote tumor specific immune responses using CD4+ and CD8+ T cells from transgenic mice expressing OVA-specific TCR to track specific cellular interactions in vivo using the same approach that we used for studying ocular tolerance (McKenna, K.C., Y. Xu, and J.A. Kapp. J. Immunol. 169:5630-5637, 2002). If noscapine serves as an adjuvant, it may be used clinically to augment endogenous immune responses in tumor bearing recipients or in conjunction with tumor vaccines. Augmentation of anti-tumor immunity would be particularly valuable in preventing metastasis of the original tumor or re-emergence of a dormant tumor.


Christopher Klug, PhD   Dr. Klug's laboratory focuses on a number of interrelated projects that deal with the genetic control of hematopoietic stem cell (HSC) self-renewal and differentiation and how normal developmental programs are subverted in the context of acute leukemias. They are also interested in understanding the underlying molecular events that control lineage commitment decisions within the hematopoietic system. The regulatory factors that are under current investigation for controlling lymphoid-lineage specification from HSC include the interleukin 7 receptor, early B-cell factor and Pax5. Acute leukemia is studied by introducing commonly observed chromosomal translocations into mouse stem cells using retroviral vectors. Two of the translocations that we have modeled in mice, the inv(16) and the t(8;21), are found in 25% of acute myeloid leukemia (AML) cases in man. AML accounts for 80% of all human acute leukemia and is thought to be a disease that is sustained by an abnormal HSC population that also bears the translocation. In a recently published paper, we have shown that the t(8;21) translocation causes HSC to expand in vivo to numbers that are 30-fold greater than what is typically seen in normal mice. Current efforts are underway to understand how the t(8;21) is affecting HSC self-renewal using microarrays and RNA interference technologies. The group is also beginning to use animal models to test the efficacy of novel treatment approaches to acute leukemia.


Lawrence S. Lamb, Jr., PhD Dr Lawrence Lamb is a Clinical Laboratory Immunologist and Associate Professor of Medicine specializing in transplantation immunology. He also is boarded by the Oncology Nursing Certification Corporation for Advanced Practice in Oncology Nursing (AOCNS). Dr. Lamb directs the UAB Cellular Therapy and Immunodiagnostics Laboratory and is Associate Director of the UAB Hospital Hematopoietic Stem Cell Transplantation Facility. His group was the first to describe an association between gamma/delta T cell recovery and disease-free survival in allogeneic bone marrow transplantation patients as well as gamma/delta T cell receptor CDR3 conservation in leukemia patients. He currently directs a research program for evaluation and translation of innate immune system-based therapies for Glioblastoma Multiforme and is funded by the NINDS (5R21NS57341), NCI (2 P50 CA097247- SPORE developmental project), and holds the National Brain Tumor Society’s Samuel Gershon Leadership Chair for Glioblastoma Research for 2007-2009. The laboratory has recently published that gamma/delta T cell numbers are significantly reduced in GBM patients and their function is substantially impaired (Bryant et al, Neuro-Oncology 2009 e-pub ahead of print), although activated gamma/delta T cells from healthy volunteers are highly cytotoxic to GBM cell lines and primary tumors. In a recently submitted manuscript we also show that GBM lines and primary tumors express several NKG2D ligands that are recognized and by gamma/delta T cells and that immunodeficient mice bearing human GBM intracranial xenografted tumors show improved survival when treated with ex vivo activated gamma/delta T cells. The laboratory is currently exploring receptor-ligand interactions between GBM and gamma/delta T cell subsets, the role of CMV in the innate response to GBM, and the design of an effective cell therapy product for clinical trials of gamma/delta T cell immunotherapy of GBM.


Robin G. Lorenz, MD, PhD   The focus of research in our laboratory is the study of the cellular components of the mucosal immune system and their interactions with the gastrointestinal epithelium, the GI microbiome, and the systemic immune response. Our first area of interest is the cellular immune response to Helicobacter in a mouse model of gastric infection and inflammation. The bacteria Helicobacter pylori is a major pathogen which is linked to acute and chronic gastritis and adenocarcinoma. It is also linked to protection from esophageal cancers and allergic asthma. We are currently investigating the interactions between gastric Helicobacter infection and asthma susceptibility in a mouse model of lung inflammation.

The second area of focus in our laboratory is the role of the intestinal epithelium and innate immune responses in the development of inflammatory bowel disease (IBD). The chronic intestinal inflammation that characterizes IBD is the result of a poorly controlled mucosal immune response to normal intestinal microbiota. The mechanisms that initiate this aberrant response are not well elucidated; however, one possibility is that a change in the intestinal epithelial barrier results in increased systemic exposure to microbial products. The P-glycoprotein (mdr1a-/-) deficient mouse is a unique model of spontaneous colitis that demonstrates an increase in colonic epithelial permeability, as well as a change in the sensitivity of toll-like receptors (TLRs) to bacterial products. Our laboratory focuses on investigating the relationships between the membrane pump- P-glycoprotein, microbial sensors-such as TLRs, and IBD. These studies utilize both in vivo models of IBD, as well as in vitro primary and continuous epithelial cell culture systems. The understanding of the basic mechanisms by which the host maintains intestinal homeostasis and barrier integrity will lay the foundation for future studies on the regulation of the inflammatory response and the design of therapies for human IBD.

The third focus of our laboratory is the influence of mucosal immune factors on the risk of type 1 diabetes development. The incidence of autoimmune Type I Diabetes (T1D) in both human patients and animal models is altered by genetic and environmental factors. These factors include an increased incidence after exposure to high fat diets and hygienic environments. These environmental effects are reproduced in the NOD mouse model of disease, where animals raised in a sterile environment have an increased incidence of disease. In addition to diabetic effects, these environmental exposures have in common the fact that they alter two components of the gastrointestinal (GI) ecosystem, the resident microbiota and the intestinal immune response. Our research focuses on the interrelationship between the GI microbiota, the intestinal immune response, and the risk of T1D development in the NOD mouse model.


Joseph Murphy, PhD Dr. Murphy's specific interests are in: (a) Symbiotic relationship between cancer and angiogenesis; (b) Immune modulation as a means of anti-cancer and anti-angiogenic therapy; (c) Microarray analysis and target validation; (d) Cyclooxygenase mediation of angiogenesis and cancer; (e) Integrin modulation of angiogenesis; (f) Endothelial cell adhesion molecules involved in leukocyte adhesion and angiogenesis; (g) Enzyme-linked immunosorbent assay development for early detection of cancer.


Laura Timares, PhD My lab is interested in understanding aspects of cutaneous immunology and carcinogenesis. Most of my research has focused on understanding the biology of skin-resident antigen presenting dendritic cells (DCs), termed Langerhans cells (LCs), with the aim of targeting them for the development of “next generation” topical vaccines. Depending on the environmental cues they receive at the affected skin site, LCs can initiate either tolerogenic or immunogenic adaptive immune responses.

Recently, we discovered that murine LCs specifically undergo cell death following successful activation of antigen-specific naïve CD4+ T cells, which limits their immunogenic potential. We have shown that LC apoptosis depends on the pro-apoptotic Bcl-2 family molecule BID; BID-deficient LCs are resistant to CD4+ T cell-induced death as well as mechanisms of UV radiation-induced tolerance and are highly immunogenic. How such apoptosis-resistant DCs induce enhanced T cell responses, evade induction of regulatory T cell (Treg) development, and how T cells trigger DC death are under investigation. Using engineered LC-deficient mouse strains, we are investigating LCs role in mediating tolerance and in promoting or protecting against skin carcinogenesis.

We have genetically engineered DCs and DNA-based “epitope-focused” vaccines to test whether we can bolster immune surveillance effectors that can block carcinogen-induced tumors at early stages. These engineered vaccines can induce antigen-specific immunity to a single point mutation, which boosts immune-surveillance and partially prevents the formation of carcinogen-induced skin tumors. These results have encouraged us to develop humanized vaccines to test in translational studies in a select group of high-risk patient populations (in collaboration with Dr. C.A. Elmets).

A relatively new area of research is in defining molecular mechanisms that drive cell transformation. We are developing new murine models of spontaneous melanoma with the aim of elucidating the role of immune-modulatory factors in regulating melanoma initiation and progression, and to identify oncogene mutations that may model human melanoma and test their potential as protective epitope-focused vaccines. In other studies, we have found that a novel pro-survival isoform of the pro-apoptotic molecule BID is associated with repair functions in cycling keratinocytes damaged by UV radiation. The opposing functions, defined by differential post-translational modifications of BID, are reminiscent of modifications that regulate p53, the “master regulator” of cell fate. We are working with Dr. M. Athar to explore potential cooperative mechanisms that may exist between BID and p53, with the hope of defining interdependencies that might be exploited for treating or inhibiting cancer initiation, growth and/or progression.


Nabiha Yusuf, PhD Our laboratory is involved in evaluating the effect of environmental influences such as chemical carcinogens and ultraviolet radiation on the skin immune system. The focus of our research is on the role of innate immunity in the development of skin carcinogenesis. Toll-like receptors (TLRs), one component of innate immunity, are intricately associated with a number of dermatologic conditions. We have found that the innate immune system mediates through Toll like receptor-4 (TLR4) signaling to activate the cell mediated adaptive immune response against chemically induced tumors. TLR4 signaling had a protective effect against 7,12-dimethylbenz(a)anthracene (DMBA) induced skin cancer in certain strains of mice which develop cell mediated immune response to this chemical carcinogen. We are currently in the process of evaluating the role of innate immune system in ultraviolet B (UVB) radiation induced skin cancer. The mechanisms by which UVB radiation influences cell-mediated immune responses have been the subject of extensive investigation.  However, there is little information on the role of innate immunity in this process. Our recent experiments suggest that certain components of innate immunity, especially TLR4, may play an important role in photoimmunosuppression. Currently, we are investigating whether the resistance of TLR4 gene knockout mice to UVB-induced immunosuppression has implications for photocarcinogenesis.  The ultimate goal of these studies will be to define the role of TLR4 in the development of immune suppression and tumor development that occurs following UV radiation.  This may allow us to identify genetic loci that are involved in these processes and to develop immunopreventive and immunotherapeutic approaches towards them.