Advanced Discovery Award (ADA) Recipients
Kathleen M. Mahoney, MD, PhD – Dana-Farber Cancer Institute, Beth Israel-Deaconess Medical Center
Gordon J. Freeman, PhD – Dana-Farber Cancer Institute
Rupal S. Bhatt, MD, PhD – Beth Israel-Deaconess Medical Center
HHLA2/KIR3DL3 as a novel therapeutic immune checkpoint pathway in renal cancer
This research team will explore a novel immune checkpoint pathway that is similar to, but non-overlapping with, the PD-1/PD-L1 pathway, which has been the key driver of advances in immunotherapy that led to much improved outcomes for many patients with cancer. A better understanding of how this HHLA2/KIR3DL3 pathway works and determining if disrupting it allows immune cells to target and destroy cancer cells could be particularly important for patients with metastatic renal cell carcinoma (RCC) who might not benefit from existing immunotherapies.
Eric Jonasch, MD – The University of Texas MD Anderson Cancer Center
Guang Peng, PhD – The University of Texas MD Anderson Cancer Center
S-phase DNA damage response links genomic instability mechanisms to anti-tumor immunity in renal cell carcinoma
This research team will investigate how the novel tumor suppressor gene NPRL2 functions. The team will study how NPRL2 triggers innate immune response in RCC through impairing S-phase DNA damage response (S-DDR). NPRL2 is frequently deleted from chromosomes in clear cell renal cell carcinoma (ccRCC) and the research team will also explore treatment strategies exploiting this deficiency.
Young Investigator Award (YIA) Recipients
Scott M. Haake, MD – Vanderbilt University Medical Center
W. Kimryn Rathmell, MD, PhD (Mentor) – Vanderbilt University Medical Center
Endogenous retrovirus expression drives immunogenicity of papillary renal cell carcinoma
In prior published work, Dr. Haake and colleagues established that endogenous retroviruses (ERVs) are a biomarker for immune response in ccRCC patients and a potential therapeutic target. This research project will shift focus to investigate ERV expression in papillary RCC (both type 1 and 2) to and how ERV impacts anti-tumor immune response in this understudied RCC subtype.
Akash Kumar Kaushik, PhD – University of Texas Southwestern Medical Center
Ralph J. DeBerardinis, MD, PhD (Mentor) – University of Texas Southwestern Medical Center
In vivo glutamine metabolism in VHL and FH mutant renal cell carcinoma
Dr. Kaushik’s research project will take a closer look at the amino acid glutamine – a major source of energy and growth for some cancer cells – and its role in cellular activity. In particular, Dr. Kaushik will investigate the efficacy of a glutaminase inhibitor in patient-derived mouse models with mutated versions of the VHL and FH tumor suppressor genes. He will also examine how effective specific inhibitors of a key energy-generating cellular process are in VHL- and FH-mutant tumors.
Ed Reznik, PhD – Memorial Sloan Kettering Cancer Center
A. Ari Hakimi, MD (Mentor) – Memorial Sloan Kettering Cancer Center
Metabolic determinants of the tumor microenvironment and sensitivity to immunotherapy in ccRCC
The tumor microenvironment (TME), which includes blood vessels, stroma, immune and other types of cells, and signaling molecules, plays an important part in in the effectiveness of immunotherapy. Dr. Reznik will closely examine tumor metabolism as it relates to the TME of ccRCC. A better understanding of the TME and its varied components might help indicate which therapies are more likely to be effective for patients with ccRCC, thereby avoiding potentially unnecessary treatment. The findings also have the potential to identify new therapeutic targets.
Tian Zhang, MD, MHS – Duke Cancer Institute
Daniel J. George, MD (Mentor) – Duke Cancer Institute
Immune correlates of immunotherapy responses in renal cell carcinoma
Patients with metastatic ccRCC have several options when it comes to first-line immunotherapy, including combination treatment with VEGF inhibitors that stop blood vessels from growing excessively. Choosing between options is still a challenge. Dr. Zhang will analyze how the TME responds to immunotherapy. In addition, Dr. Zhang will investigate a panel of five genes and its association with resistance to ipilimumab/nivolumab combination therapy.