# NIH grant: Nociceptive control of bladder tumorigenesis (1R01CA312146-01) — retained record

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source: [us-gov-api](https://highsignal.app/data/us-gov-api) (us-gov-api:nih-reporter)  published 2026-06-26 00:00 ingested 2026-06-29 10:35

[original source ↗](https://reporter.nih.gov/project-details/1R01CA312146-01)

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NIH grant 1R01CA312146-01: Nociceptive control of bladder tumorigenesis
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: ULRICH H VON ANDRIAN. Award: $688893.
Start: 2026-06-26T00:00:00.
Despite recent advances in the treatment of malignant diseases, bladder cancer continues to
represent a significant unmet clinical need. Nociceptors - sensory neurons that trigger the
sensation of pain or itch in response to noxious stimuli - can affect immune response in various
contexts; however, their role in the pathobiology of bladder cancer remains unexplored.
Preliminary work for this project employing an orthotopic mouse model of non-muscle invasive
bladder cancer (NMIBC) revealed that bladder tumors are densely innervated by nociceptors.
Furthermore, pharmacologic nociceptor ablation or chemogenetic inhibition of nociceptor
electrical activity resulted in immune-mediated tumor rejection. Pilot studies examining cocultures
of monocytes and dorsal root ganglion-derived nociceptors indicate that nociceptors
rapidly induce monocyte differentiation into immunosuppressive myeloid-derived suppressor
cells (MDSCs). Accordingly, monocyte-derived MDSCs were the first immune cells to populate
incipient bladder cancer lesions and represented the most abundant immune cell type in
advanced tumor-bearing urinary bladders. Collectively, these preliminary findings suggest that
NMIBC may exploit an immunosuppressive neuro-immune axis to evade anti-tumor immune
responses and identify nociceptive nerve fibers as potential targets for the treatment or
prevention of bladder cancer. To test this hypothesis, Aim 1 will build on these initial
observations to fully explore the effect of nociceptors on primary urinary bladder carcinomas
and metastatic disease. Aim 2 will define the molecular mechanisms and consequences of the
three-way communication between bladder tumor cells, nociceptive fibers, and immune cells.
The proposed research plan will rigorously dissect a complex multi-step process involving
dynamic interactions between malignant cancer cells, nociceptors, monocytes, and T cells that
occur in a highly time-dependent manner within the tumor and the surrounding bladder tissue,
as well as in draining lymph nodes and in the blood circulation. To accomplish this research, the
use of live mice is essential because there are currently no in vitro or in silico alternatives that
could accurately recapitulate this complex multi-system process in its entirety. In aggregate, the
proposed work will dissect the role of nociceptors in the pathogenesis of NMIBC, identify the
immune cells within the tumor microenvironment that are controled by nociceptors, and
determine the molecular means of nociceptor-immune cell communication. Thus, given the high
unmet need for better therapies for bladder cancer, this work is highly significant.
```



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