Post-doctoral Fellowship Grant Awarded to Janghyun Park

Developing immunotherapy for DIPG/DMG (Diffuse Intrinsic Pontine Glioma/Diffuse Midline
Glioma) has been particularly difficult because of the unique characteristics of these brain
tumors, such as their low infiltration by immune cells. To create more effective immunotherapies,
we need to understand where and how the body mounts an immune response to these tumors.
Traditionally, lymph nodes were considered the primary sites for initiating immune responses.
However, my research has unexpectedly found that the bone marrow in the occipital skull—the
site where immune cells are produced—contains specialized clusters that can recognize brain
diseases, functioning similarly to lymph nodes. I propose that the immune response against
DIPG/DMG primarily takes place in the skull bone marrow. I believe the skull bone marrow
might control the immune response against tumors by producing antibodies that specifically
target them. To investigate this, I will use advanced tools like high-resolution microscopy, flow
cytometry, and bioinformatics with a genetic model of DIPG/DMG. Furthermore, I hypothesize
that the skull bone marrow could be a novel target for immunotherapy. I will test whether
boosting immune cells in the skull bone marrow provides therapeutic benefits in a mouse model
of DIPG/DMG. This study aims to expand our understanding of how immune responses to
DIPG/DMG are generated. Additionally, the skull bone marrow could serve as a new approach
for diagnosis, prognosis, and identifying tumor subtypes and immune profiles that predict
responses to immunotherapy. By specifically targeting the skull bone marrow, we can potentially
develop more effective immunotherapies with fewer side effects. This approach could be applied
to various types of immunotherapy, including vaccines, immune checkpoint inhibitors, and
engineered cell therapies.