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Myeloid cell-derived interleukin 1b promotes chemoresistance in metastatic ovarian cancer

Award Number: R21CA297425
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/03/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Myeloid cell-derived interleukin 1b promotes chemoresistance in metastatic ovarian cancer - PROJECT SUMMARY Most ovarian cancer (OC) patients respond to the front-line chemotherapy but succumb to chemoresistant relapse with peritoneal metastases. How chemoresistance develops in OC patients after the front-line chemotherapy remains poorly understood. Recent understanding of the tumor immune microenvironment (TIME) suggests that inflammatory mediators from myeloid cells play key roles in developing chemoresistance. This proposal seeks to understand whether and how a classical inflammatory mediator from myeloid cells, interleukin 1β (IL1β), promotes OC chemoresistance, aiming to eradicate metastatic OC by overcoming IL1β-mediated chemoresistance. Based on published and our preliminary results, we hypothesize that myeloid cell-derived IL1β promotes chemoresistance in metastatic OC by modifying TIME via activation of OC cells and fibroblasts; combining IL1β neutralization and chemotherapy eliminates chemoresistant OC. This will be tested with the following Aims. Aim 1: Test the hypothesis that the combination of chemotherapy and IL1β neutralization overcomes OC chemoresistance. Aim 2: Test the hypothesis that myeloid cell-derived IL1β drives OC chemoresistance by modifying TIME. Aim 3: Test the hypothesis that myeloid-derived IL1β promotes formation of chemoresistant spheroids.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $473,624 )
2026	2026	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Treatment Research	000	1	4/3/2026	NEW	$473,624
														Subtotal = $473,624

Grand Total All Awards = $473,624

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Myeloid cell-derived interleukin 1b promotes chemoresistance in metastatic ovarian cancer

Award Number: R21CA297425

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/03/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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