Abstract Details

Title Inflammatory signaling supports cancer cell growth within the leptomeninges

Topic Neuro-oncology

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 7-024

Objective NA

Background Inflammatory cell infiltrate is a pathologic hallmark of leptomeningeal metastasis (LM). The mechanistic role that this infiltrate might play in the pathogenesis of LM remains unexplored.

Design/Methods We have employed multiple, orthogonal analyses of iteratively sampled CSF specimens from patients harboring LM from breast and lung primary cancers to identify key molecular components of LM. We have dissected cell-cell signaling through use of syngeneic mouse models of LM.

Results Flow cytometic analysis of 15 specimens demonstrates a cellular environment dominated by activated macrophages; Cytokine arrays from these samples reveal predominantly pro-inflammatory cytokines including IL-6, IL-8 and IL-1b. Single cell RNASeq of fresh CSF specimens from six patients shows that inflammatory signals from leptomeningeal macrophages induce NFKB signaling and production of lipocalin-2 (LCN2) in the cancer cells. In syngeneic mouse models of LM, we find thatcancer cells competent to inhabit the leptomeninges generate LCN2 in response to NFKB activation. Further, we find that LCN2 is both necessary and sufficient to support cancer cell growth in the leptomeninges in vivo. Pharmacologic interference with LCN2 signaling suppressed LM in these preclinical models.

Conclusions This bench-to-bedside strategy has uncovered key interactions between metastatic cancer and the innate immune system, suggesting novel, orthogonal therapeutic approaches to leptomeningeal metastasis.

Authors/Disclosures
Adrienne Boire, MD, PhD, FAAN (Memorial Sloan-Kettering) PRESENTER	The institution of Dr. Boire has received research support from National Cancer Institute. The institution of Dr. Boire has received research support from Center for Experimental Therapeutics. The institution of Dr. Boire has received research support from STARR Cancer Consortium. The institution of Dr. Boire has received research support from National Cancer Institute. The institution of Dr. Boire has received research support from Break Through Cancer. The institution of Dr. Boire has received research support from Mary Kay Ash Foundation. The institution of Dr. Boire has received research support from American Cancer Society. The institution of Dr. Boire has received research support from Melanoma Research Alliance. Dr. Boire has received intellectual property interests from a discovery or technology relating to health care. Dr. Boire has received intellectual property interests from a discovery or technology relating to health care. Dr. Boire has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Elena Pentsova, MD (Memorial Sloan-Kettering Cancer Center)	The institution of Dr. Pentsova has received research support from YmAbs Therapeutics, Inc.
	No disclosure on file
	No disclosure on file

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