This Project Grant award of $635,173 from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) supports research to characterize the immune cell recruitment and immunosuppression mechanisms driven by the CKLF1 chemokine in MYCN-driven neuroblastoma. The award will leverage the zebrafish neuroblastoma model, patient sample analyses, in vitro co-culture systems, and mouse models to...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) will fund a study to characterize the neuro-immune interactions in the skin of tumor-bearing mice with oxaliplatin-induced peripheral neuropathy (OIPN). The $426,960 award, with a project period from Sep 1, 2024 to Nov 30, 2026, will be performed by Wake Forest University Health Sciences. The study aims to (i) define how the cutaneous immune landscape is activated by tumor and repeated...
The National Cancer Institute (NCI) awarded a 3-year, $183,398 Project Grant to The Ohio State University under the Cancer Research Manpower (CFDA 93.398) program. The goal of the project is to elucidate the mechanisms by which tumor hypoxia (low oxygen) contributes to immune privilege and treatment resistance in non-small cell lung cancer (NSCLC) tumors. The researchers will investigate the use of mitochondrial inhibitors, such as papaverine (PPV) and SMV-32, to reoxygenate the NSCLC tumor...
This federal Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $702,748 to Weill Medical College of Cornell University to research the role of neutrophils in anti-tumor immunity and immune-related adverse events associated with T cell-based cancer immunotherapies. The key objectives are to: 1) characterize the gene pathways and tumor-derived factors that define functional subsets of anti-tumorigenic neutrophils, 2) identify the clinically...
This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, provides $628,373 to The General Hospital Corporation, doing business as Massachusetts General Hospital (MGH), to conduct research on understanding how endogenous dendritic cells drive T cell activation and expansion in glioblastoma. The award period runs from August 1, 2025 to June 30,...
This $431,968 Project Grant award from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) supports research by Baylor College of Medicine to elucidate how the oncogene MYCN rewires the metabolic environment of neuroblastoma tumors to drive immune suppression, and to modulate this metabolic environment to enhance immune-based approaches for high-risk MYCN-amplified neuroblastoma. The research aims to uncover how MYCN amplification, a driver of aggressive neuroblastoma,...
This $509,448 Project Grant award from the National Cancer Institute (CFDA 93.398 - Cancer Research Manpower program) supports research by The Leland Stanford Junior University to investigate antigen-presenting cells in lymph nodes and their role in modulating metastatic tumor progression. The key objectives are to: 1) identify the specific antigen-presenting cell populations responsible for promoting tumor-specific regulatory T cell development, and 2) assess therapeutic strategies to reprogram...
This Project Grant award from the National Cancer Institute (NCI), under the Cancer Research Manpower (CFDA 93.398) program, provides $281,606 to New York University School of Medicine to conduct research aimed at harnessing gut-derived bacteria to drive anti-tumor immunity in lung cancer. The 5-year project, led by Dr. Rabi Upadhyay, an Assistant Professor at NYU, will investigate the mechanism by which certain gut commensals can trigger systemic anti-tumor immune responses, even in the absence...
This $195,896 Project Grant, awarded by the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, supports research to define the circuit connectivity between glioblastoma, a fatal brain cancer, and diverse neuronal populations in the mouse brain. The research aims to elucidate the role of cholinergic neuromodulatory inputs in regulating glioma progression, with the goal of...
The National Cancer Institute (NCI) awarded a $619,628 Project Grant under the Cancer Biology Research program (CFDA 93.396) to The Trustees of the University of Pennsylvania, doing business as Clinical Practices of the University of Pennsylvania. The funding will support the development and validation of an autologous mouse model to study immune system interactions with glioblastoma, a type of brain cancer. The goal is to create a humanized mouse system that incorporates patient-derived tumor...
DISSECTING NEURO-IMMUNE INTERACTIONS IN CANCER - PROJECT SUMMARY/ABSTRACT: CANCER IS HIGHLY ADEPT AT EXPLOITING NORMAL PHYSIOLOGICAL FUNCTIONS TO SUPPORT ITS GROWTH. ONE IMPORTANT COMPONENT OF TISSUE PHYSIOLOGY IS NEURONS WHICH WEAVE THROUGH OUR ORGANS, RELEASING NEUROPEPTIDES INTO NEARBY TISSUE. IMPORTANTLY, THE ROLE INNERVATION PLAYS IN MALIGNANCY AND ANTI-TUMOR IMMUNITY REMAINS LARGELY UNKNOWN AND UNDERSTUDIED. OUR PRELIMINARY ANALYSIS SHOWS THAT TUMOR INFILTRATING IMMUNE CELLS EXPRESS HIGH LEVELS OF RECEPTORS FOR SENSORY NEUROPEPTIDES, WHICH FURTHER POSITIVELY CORRELATES WITH EXPRESSION OF GENES ASSOCIATED WITH IMMUNE CELL DYSFUNCTION. THESE DATA SUGGEST THAT INNERVATION MAY PLAY AN IMPORTANT ROLE IN REGULATING ANTI-TUMOR IMMUNITY. TO TEST THIS HYPOTHESIS, WE PROPOSE STRATEGIES TO INVESTIGATE THE ROLE OF INNERVATION IN CANCER, AND TO DETERMINE HOW NEUROPEPTIDE SENSING ON IMMUNE CELLS IMPACTS ANTI-TUMOR IMMUNITY IN THE FOLLOWING OBJECTIVES: OBJECTIVES OF UNNERVING CANCER: (1) INVESTIGATE THE DEGREE OF SENSORY NEURON INNERVATION IN CANCER (2) DETERMINE HOW NEUROPEPTIDE SENSING ON DCS IMPACTS ANTI- TUMOR IMMUNE RESPONSES. USING REPORTER TOOLS AND MULTIPLEXED IMAGING, WE WILL DETERMINE INNERVATION OF TUMOR TISSUES IN PRE-CLINICAL MODELS AND PATIENT SAMPLES. BUILDING ON OUR RESULTS, WE WILL INVESTIGATE THE FUNCTIONAL AND TRANSCRIPTIONAL EFFECTS OF NEUROPEPTIDE SENSING ON IMMUNE POPULATIONS USING ENDOGENOUS AND SYNGENEIC MODELS. RESULTS FROM THIS PROJECT HAVE THE POTENTIAL TO SIGNIFICANTLY ADVANCE OUR CURRENT UNDERSTANDING OF THE NERVOUS SYSTEM'S CONTRIBUTION TO CANCER. THERAPEUTICALLY, EXPLOITING THE NEURONAL VULNERABILITY OF CANCER USING EXISTING CLINICALLY APPROVED NEUROMODULATORS HAS THE POTENTIAL TO RAPIDLY TRANSLATE CLINICALLY FOR THE PREVENTION AND TREATMENT OF CANCER. THE LEGACY OF THIS NCI FUNDED INTERDISCIPLINARY RESEARCH WILL BE TO UNDERSTAND THE NEURO- IMMUNE COMMUNICATION IN CANCER, OPENING DOORS FOR NOVEL THERAPEUTIC STRATEGIES. KEYWORDS: TUMOR IMMUNOLOGY, IMMUNOTHERAPY, CANCER NEUROSCIENCE, DENDRITIC CELLS, NEURO-IMMUNE INTERACTIONS GRAPHICAL ABSTRACT: TUMOR INNERVATION CORRELATES WITH POOR SURVIVAL IN SEVERAL TUMOURS. I PROPOSE TO STUDY NEURONAL DENSITY IN SKIN AND LUNG TUMOUR, AND QUERY CORRELATION OF NEURONAL DENSITY TO THERAPEUTIC RESPONSES. I HYPOTHESISE THAT SENSORY NEURONS RELEASE NEUROPEPTIDES, INCLUDING CGRP, WHICH ACTS ON RECEPTOR EXPRESSING DENDRITIC CELLS (DCS). TOGETHER THIS LEADS TO BLUNTED DC RESPONSES PERPETUATING CD8+ T CELL DYSFUNCTION AND TUMOR PROGRESSION. OBJECTIVE 1 OBJECTIVE 2