Masanobu Komatsu
Johns Hopkins University, MD·Microbiology & Immunology
Immune checkpoint inhibitors are drugs that release the brakes on the immune system, and they work for only some cancer patients. A key reason is that T cells and B cells, the immune cells that attack tumors, are often shut out of the tumor.
- Fields
Microbiology & Immunology
Biology
Medicine & Clinical Research
- Topics
high endothelial venules
tumor immunity
cancer immunotherapy
- Grants
- 1 known grant, through Mar 2027
What they work on
- Test whether the signaling protein R-Ras in blood vessel cells drives the formation of high endothelial venules in tumors, using mice that lack or overproduce endothelial R-Ras in mammary tumor and melanoma models.
- Determine how tumor HEVs change the entry of T cells, B cells and dendritic cells and the cytokine environment, using immunofluorescence, ELISA, flow cytometry and RNA sequencing, and confirm findings in human cancer specimens.
- Characterize tumor HEV function and test whether T cells recruited through them are activated inside the tumor, by transferring naive OT-1 T cells into mice bearing tumors that express the OVA antigen.
- Determine how intratumoral HEVs affect immune destruction of tumors and the response to PD-1/PD-L1 checkpoint inhibition therapy in mouse tumor models.
More about the research
High endothelial venules (HEVs) are specialized small blood vessels that normally act as entry gates for immune cells into lymph nodes. They can also form inside tumors, and patients whose tumors contain many HEVs tend to do better. This project asks whether building more of these gateways inside tumors could let immune cells in and make immunotherapy work for more people.
Why it matters
Many cancer patients do not benefit from immune checkpoint inhibitors because immune cells cannot get into their tumors. If tumor HEVs prove to be the gateways that let T and B cells in, they could become new targets for turning "cold" tumors into ones that respond to immunotherapy. The project aims to provide proof of concept for this idea, which could eventually help more patients with cancers such as breast cancer and melanoma respond to PD-1/PD-L1 therapy.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Sana D Karam
Washington University in St Louis, MO·Microbiology & Immunology
Determine how immune checkpoint inhibitors such as anti-PD-L1 drugs act on PD-1-expressing regulatory T cells and their STAT3 signaling during radiation therapy, using genetically engineered mice and samples from HNSCC clinical trials.
Andrew Dudley
University of Virginia, VA·Microbiology & Immunology
Test whether deleting Dnmt1, a DNA-methylating enzyme that silences genes, in blood vessel lining cells produces durable melanoma control by promoting dendritic cell trafficking to tumor-draining lymph nodes and recruiting CD4+ T cells, using genetic mouse models and immune profiling by flow cytometry.
Jun Wang
New York University, NY·Microbiology & Immunology
Determine whether Siglec-15, a tumor-associated immune brake, also suppresses myeloid cells such as macrophages, and identify the receptors it binds on myeloid cells and T cells.
The school
Johns Hopkins University: 100 labs on PI Pages, $4.1B a year on research, 622 research doctorates a year.
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