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June 12, 2018 | 5:00 p.m. - 7:00 p.m.
Category: Seminar
Location: CS Mott Center for Human Growth and Development #103
Cost: Free
Audience: Current Graduate Students, Faculty, Invite Only

The campus community is invited to the next Genomics@Wayne seminar on June 12, 2018. The speaker will be Donovan Watza.

Dr. Watza will present, " Genomic Analysis of the Naturally Occurring Variation in Patient Outcomes Reveals Potential Candidates for Immunotherapeutic Intervention."

ABSTRACT:

Lung cancer is the second most incident and leading cause of cancer mortality in the United States [1]. Lung tumors characteristically contain a significant number of somatic mutations, only surpassed in total somatic mutation burden by cancers of the skin [2]. Moreover, somatic mutations which occur within the exome often result in mutation associated neo-antigens (MANAs), antigens which serve as the targets of anti-tumor immune responses. Consequently, lung cancer should be an excellent candidate for immunotherapeutic treatment owing to its substantial mutation signature, yet previously proven immunotherapies in other high mutational signature cancer types have shown limited success in the treatment of lung tumors and only PD-1/PD-L1 agents are approved for use in this disease[3,4].

Our central hypothesis is that immune-centric factors differentially affect lung cancer prognosis and their identification through the study of natural variation in patient outcomes will provide high-value candidates for advancing immunotherapy in lung cancer. Resources provided by the Schwartz lab under the INHALE study [5] will be utilized to conduct this study. To identify novel candidates in lung tumors with immunotherapeutic value, we are conducting a comprehensive investigation into the ways in which immune-phenotypes in a large genetic cohort of lung cancer patients may modulate tumor-immune interactions and impact the natural course of disease. This study will utilize germline genetic profiling, tumor transcriptome profiling, and the delineation of the immunological state of the tumor microenvironment using immunohistochemistry and computational deconvolution in primary lung specimens, all in association with patient survival. Validation efforts are currently underway on several lung cancer cohorts including the TCGA lung cohort to replicate results from these analyses. As a physician-scientist in training, this thesis work will provide a substantial foundation to practice independent translational and clinical research in the future as a clinician-scientist.

Impact: The identification of the genetic and molecular immunologic profiles of lung cancer and their contribution to patient prognosis will isolate new candidates for drug targeting to improve patient outcomes in lung cancer through the advancement of immunotherapy.

References

1. Siegel RL, KD Miller and A Jemal, Cancer statistics, 2018. CA: A Cancer Journal for   Clinicians, 2018. 68(1): p. 7-30.

2.  Chalmers ZR, et al., Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Medicine, 2017. 9(1): p. 34.

3.  Rizvi NA, et al., Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science, 2015. 348(6230): p. 124-128.

4.  Khalil DN, et al., The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nature Reviews Clinical Oncology, 2016. 13: p. 273.

5. Schwartz AG, et al., Risk of Lung Cancer Associated with COPD Phenotype Based on Quantitative Image Analysis. Cancer Epidemiology Biomarkers & Prevention, 2016.

 

For more information about this event, please contact Dawn Cochrane at 313-577-0502 or ac9777@wayne.edu.