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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.
• • • •
Research Team:
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 under-
studied 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. KCJ
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