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Landon Foundation-AACR INNOVATOR Award for Cancer Immunology Research

The Landon Foundation-AACR INNOVATOR Award for Cancer Immunology Research was established to recognize the outstanding achievement of a junior faculty-level scientist working in the field of cancer immunology, and support his or her research that, if successful, will have potential to advance our basic knowledge of tumor immunology mechanisms, or develop new concepts in the treatment, control, or prevention of cancer by immunology-based therapeutic approaches. The goal of the grant program is to encourage junior faculty who are in the first five years of a faculty appointment (at the start of the grant term) to pursue novel cancer immunology research. Travel support is included to help foster interactions and collaborations among cancer scientists studying various aspects of cancer biology and to disseminate scientific knowledge about cancer immunology research within the field. Proposed projects may be basic, translational, clinical, or epidemiological in nature and must focus on cancer immunology; including, but not limited to, immune recognition, regulation, tumor escape, and therapeutic manipulation.

2014 Grantee

Yvonne M. Saenger, MDYvonne M. Saenger, MD
Assistant Professor, Department of Hematology and Oncology
Mt. Sinai Icahn School of Medicine
New York, New York
Proving Immune Signatures in High Risk Primary Melanoma Tumors to Establish Prognostic Biomarkers and Mechanisms of Successful Immune Surveillance

Dr. Yvonne Saenger’s research focuses on molecular phenotyping of the immune microenvironment in melanoma tumors to define prognostic biomarkers. Melanoma is an extremely aggressive cancer, and even completely surgically resected tumors confer mortality risk due to seeding of the body by micro-metastsis. The immune system plays a determinative role in preventing melanoma progression.  However, currently there is no reliable way to measure the quality of each patient’s individual immune response to the melanoma and thus clinicans cannot personalize follow-up and adjuvant therapy.

Dr. Saenger and her team recently employed NanoString, a very sensitive technology for quantification of RNA transcripts in formalin fixed paraffin embedded (FFPE) tissues, to define a 53-gene panel predictive of survival in stage II-III resected melanoma. Identified genes in the 53-gene panel play key roles in lymphocyte activation, interferon signaling, and antigen presentation, highlighting the importance of immune-surveillance mechanisms.  Dr. Saenger’s approach focuses on developing the 53-gene panel as a tool with potential clinical utility by validating the panel on a large cohort of patients with prospectively gathered clinical annotation from a multicenter study. Dr. Saenger is also working to develop immunohistochemical (IHC) prognostic immune protein markers based on the NanoString RNA data. IHC is more affordable for clinical laboratories than NanoString and novel IHC markers derived from the 53-gene signature may complement existing immunopathologic methods for characterizing immune infiltration such as quantification of tumor infiltrating lymphocytes (TILs) and the immunoscore. This would allow for ICH techniques with enhanced precision for clinical prognostication.

In addition, through analysis of genomic networks, Dr. Saenger is working, in collaboration with network biologists, to define immune gene targets for therapeutic interventions and to define key immune pathways driving a favorable immune phenotype. The question then arises as to why some patients have a favorable immune gene profile with activation of key immune pathways while other patients do not.  Together with her collaborators, Dr. Saenger is also studying the genetic mutations found in the DNA of melanoma tumors to determine whether defined mutational profiles may confer a favorable immune profile.

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