Emmanuel Katsanis
Professor, BIO5 Institute
Professor, Immunobiology
Professor, Medicine
Professor, Pathology
Professor, Pediatrics
Program Director, Blood and Bone Marrow Transplant
Professor, Cancer Biology - GIDP
Primary Department
Department Affiliations
(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


Graetz, R., Meyer, R., Shehab, K., & Katsanis, E. (2018). Successful resolution of hyperammonemia following hematopoietic cell transplantation with directed treatment of Ureaplasma parvum infection. Transplant infectious disease : an official journal of the Transplantation Society.

Hyperammonemia following hematopoietic cell transplantation (HCT) has been characterized as idiopathic and is associated with a very high mortality. A causal relationship between Ureaplasma infection and hyperammonemia in immunocompromised lung transplant recipients has recently been described. We document the first case of hyperammonemia following HCT associated with Ureaplasma parvum. The initiation of appropriate antibiotics resulted in rapid resolution of hyperammonemic encephalopathy and eradication of the implicating organism. This article is protected by copyright. All rights reserved.

Alizadeh, D., Trad, M., Hanke, N. T., Larmonier, C. B., Janikashvili, N., Bonnotte, B., Katsanis, E., & Larmonier, N. (2014). Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer. Cancer research, 74(1), 104-18.

Myeloid-derived suppressor cells (MDSC) expand in tumor-bearing hosts and play a central role in cancer immune evasion by inhibiting adaptive and innate immunity. They therefore represent a major obstacle for successful cancer immunotherapy. Different strategies have thus been explored to deplete and/or inactivate MDSC in vivo. Using a murine mammary cancer model, we demonstrated that doxorubicin selectively eliminates MDSC in the spleen, blood, and tumor beds. Furthermore, residual MDSC from doxorubicin-treated mice exhibited impaired suppressive function. Importantly, the frequency of CD4(+) and CD8(+) T lymphocytes and consequently the effector lymphocytes or natural killer (NK) to suppressive MDSC ratios were significantly increased following doxorubicin treatment of tumor-bearing mice. In addition, the proportion of NK and cytotoxic T cell (CTL) expressing perforin and granzyme B and of CTL producing IFN-γ was augmented by doxorubicin administration. Of therapeutic relevance, this drug efficiently combined with Th1 or Th17 lymphocytes to suppress tumor development and metastatic disease. MDSC isolated from patients with different types of cancer were also sensitive to doxorubicin-mediated cytotoxicity in vitro. These results thus indicate that doxorubicin may be used not only as a direct cytotoxic drug against tumor cells, but also as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering the efficacy of T-cell-based immunotherapy.

Epple, L. M., Bemis, L. T., Cavanaugh, R. P., Skope, A., Mayer-Sonnenfeld, T., Frank, C., Olver, C. S., Lencioni, A. M., Dusto, N. L., Tal, A., Har-Noy, M., Lillehei, K. O., Katsanis, E., & Graner, M. W. (2013). Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 29(5), 390-8.

This paper presents the treatment of a 12-year-old female spayed Great Dane who presented with vestibular signs (ataxia, nystagmus, hind end collapse). Thoracic radiographs revealed a discrete pulmonary nodule in the right cranial lung lobe. Ultrasound-guided fine needle aspirate detected primary bronchoalveolar adenocarcinoma, verified via computed tomography, with a second smaller nodule discovered in the right cranial lung lobe.

Ramanathapuram, L. V., Hahn, T., Graner, M. W., Katsanis, E., & Akporiaye, E. T. (2006). Vesiculated alpha-tocopheryl succinate enhances the anti-tumor effect of dendritic cell vaccines. Cancer immunology, immunotherapy : CII, 55(2), 166-77.

Alpha tocopheryl succinate (alpha-TOS) is a non-toxic vitamin E analog under study for its anti-cancer properties. In an earlier study, we showed that alpha-TOS, when used in combination with non-matured dendritic cells (nmDC) to treat pre-established tumors, acts as an effective adjuvant. In this study, we have used vesiculated alpha-TOS (Valpha-TOS), a more soluble form of alpha-TOS that is relevant for clinical use, in combination with dendritic cells to treat pre-established murine tumors. We demonstrate that Valpha-TOS kills tumor cells in vitro and inhibits the growth of pre-established murine lung carcinoma (3LLD122) as effectively as alpha-TOS. The combination of Valpha-TOS plus non-matured or TNF-alpha-matured DC is more effective at inhibiting the growth of established tumors than Valpha-TOS alone. We also observed that Valpha-TOS induces expression of heat shock proteins in tumor cells and that co-incubation of non-matured DC with lysate derived from Valpha-TOS-treated tumor cells leads to DC maturation evidenced by up-regulation of co-stimulatory molecules and secretion of IL-12p70. This study therefore demonstrates the immunomodulatory properties of Valpha-TOS that may account for its adjuvant effect when combined with DC vaccines to treat established tumors.

Feng, H., Zeng, Y., Graner, M. W., Likhacheva, A., & Katsanis, E. (2003). Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity. Blood, 101(1), 245-52.

We have previously reported that apoptotic tumor cells can be either immunogenic or nonimmunogenic in vivo, depending on whether or not these cells are heat stressed before induction of apoptosis. Stressed apoptotic cells express heat shock proteins on their plasma membranes and dendritic cells are capable of distinguishing them from nonstressed apoptotic cells. Here we provide evidence that when purified heat shock protein 70 or chaperone-rich cell lysate (CRCL) from syngeneic normal tissue is used as an adjuvant with nonimmunogenic apoptotic tumor cells in vaccination, potent antitumor immunity can be generated. This antitumor immunity is mediated by T cells because antitumor effects are not observed in either severe combined immunodeficiency or T cell-depleted mice. We further demonstrate that vaccination of mice with apoptotic tumor cells mixed with liver-derived CRCL as adjuvant were capable of enhancing the production of T(H)1 cytokines, inducing specific cytotoxic T lymphocytes and eliciting long-lasting antitumor immunity. Stress proteins from autologous normal tissue components therefore can serve as danger signals to enhance the immunogenicity of apoptotic tumor cells and stimulate tumor-specific immunity