Emmanuel Katsanis

Emmanuel Katsanis

Professor, Pediatrics
Professor, Immunobiology
Professor, Medicine
Professor, Pathology
Program Director, Blood and Bone Marrow Transplant
Professor, Cancer Biology - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-7053

Work Summary

Augmenting immune responses to cancer. Reducing relapse and graft versus host disease after hematopoietic cell transplantation.

Research Interest

Dr. Emmanuel Katsanis, MD, and his laboratory conduct basic and translational research aimed at advancing new cancer immunotherapeutic strategies. His expertise is in stem cell transplant immunology, cellular therapy, and cancer vaccine approaches.Immunity against tumors depends on complex innate and adaptive immune responses that involve the sequential mobilization of 'messenger' and 'killer' immune cells. However, despite the arsenal harbored by the immune system to ensure tumor immunosurveillance, cancers can escape immune detection and elimination. Current research in the laboratory is evaluating immuno- and chemo-immunotherapeutic strategies to promote anti-tumor immune responses following bone marrow transplantation, while investigating approaches to mitigate graft versus host effects. Keywords: Cancer Immunology, Hematopoietic Cell Transplantation

Publications

Lakomy, D., Janikashvili, N., Fraszczak, J., Trad, M., Audia, S., Samson, M., Ciudad, M., Vinit, J., Vergely, C., Caillot, D., Foucher, P., Lagrost, L., Chouaib, S., Katsanis, E., Larmonier, N., & Bonnotte, B. (2011). Cytotoxic dendritic cells generated from cancer patients. Journal of immunology (Baltimore, Md. : 1950), 187(5), 2775-82.

Known for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies.

Hanke, N., Alizadeh, D., Katsanis, E., & Larmonier, N. (2013). Dendritic cell tumor killing activity and its potential applications in cancer immunotherapy. Critical reviews in immunology, 33(1), 1-21.

Universally viewed as the sentinels and messengers of the immune system and traditionally referred to as professional antigen-presenting cells, dendritic cells (DCs) play a fundamental role in antitumor immunity. DCs are uniquely equipped with the ability to acquire, process, and present to T lymphocytes tumor-derived antigens. They can drive the differentiation of naive T cells into activated tumor-specific effector lymphocytes. DCs also dictate the type and regulate the strength and duration of T-cell responses. In addition, they contribute to natural killer and natural killer T-cell antitumoral function and to B-cell-mediated immunity. Besides this cardinal role as orchestrators of innate and adaptive immune responses, many studies have provided evidence that DCs can also function as direct cytotoxic effectors against tumors. This less conventional aspect of DC function has, however, raised controversy as it relates to the origin of these cells and the induction, regulation, and mechanisms underlying their tumoricidal activity. The possible impact of the cytotoxic function of DCs on their capability to present antigens also has been the focus of intensive research. This review examines these questions and discusses the biological significance of this nontraditional property and possible strategies to exploit the killing potential of DCs in cancer immunotherapy.

McEarchern, J. A., Kobie, J. J., Mack, V., Wu, R. S., Meade-Tollin, L., Arteaga, C. L., Dumont, N., Besselsen, D., Seftor, E., Hendrix, M. J., Katsanis, E., & Akporiaye, E. T. (2001). Invasion and metastasis of a mammary tumor involves TGF-beta signaling. International journal of cancer, 91(1), 76-82.

Several studies have correlated escape from TGF-beta-mediated cell cycle arrest with the tumorigenic phenotype. Most often, this escape from growth control has been linked to dysfunctional TGF-beta receptors or defects in the TGF-beta-mediated SMAD signaling pathway. In this report, we found that highly metastatic 4T1 mammary carcinoma cells express functional TGF-beta receptors capable of initiating SMAD-mediated transcription, yet are not growth inhibited by TGF-beta1. We further observed that TGF-beta directly contributes to the metastatic behavior of this cell line. Exposure to TGF-beta caused 4T1 cells to undergo morphological changes associated with the metastatic phenotype and invade more readily through collagen coated matrices. Furthermore, expression of a dominant negative truncated type II receptor diminished TGF-beta signaling and significantly restricted the ability of 4T1 cells to establish distant metastases. Our results suggest that regardless of 4T1 resistance to TGF-beta-mediated growth inhibition, TGF-beta signaling is required for tumor invasion and metastases formation.

Okolo, O. N., Katsanis, E., Yun, S., Reveles, C. Y., & Anwer, F. (2017). Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events. Case reports in hematology, 2017, 5375793.

Objective and Importance. Cyclic neutropenia (CyN) is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk of infection. Case. A 25-year-old male diagnosed with CyN, on G-CSF but worsening quality of life. Pretransplant investigations revealed ELANE mutation positive severe CyN along with familial Mediterranean fever (MEFV) mutation. Intervention. Bone marrow transplantation as treatment for dual mutation (ELANE and MEFV mutation) positive severe CyN. Conclusion. BMT may be considered as an alternative treatment for severe CyN in patients who are refractory to G-CSF. It is postulated that in our patient the combined mutations (CyN and MEFV) may have contributed to the severity of this individual's symptoms. We suggest CyN patients who present with severe symptoms have evaluation with ELANE mutation testing, Periodic Fever Syndromes Panel, and routine marrow assessment with FISH, conventional cytogenetics, and morphological evaluation for MDS/AML.

Kanate, A. S., DiGilio, A., Ahn, K. W., Al Malki, M., Jacobsen, E., Steinberg, A., Hamerschlak, N., Kharfan-Dabaja, M., Salit, R., Ball, E., Bashir, Q., Cashen, A., Couriel, D., Diez-Martin, J., Katsanis, E., Linhares, Y., Mori, S., Nash, R., Pawarode, A., , Perales, M. A., et al. (2017). Allogeneic haematopoietic cell transplantation for extranodal natural killer/T-cell lymphoma, nasal type: a CIBMTR analysis. British journal of haematology.