Thursday, October 2, 2025 10/2/2025

Natural killer cells subvert immune checkpoint therapy of tumors

Award Number: R01CA303538
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/24/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Natural killer cells subvert immune checkpoint therapy of tumors - Abstract Since natural killer (NK) cells can kill tumor cells that also stimulate NK cell production of cytokines, there is intense current interest on how to harness NK cells to advance immunotherapy of cancer. Most strategies guiding such work focus on markedly enhancing NK cell responses to tumors. However, our understanding of NK cell biology in the context of immune checkpoint therapy (ICT) of cancer is poorly understood. Contrary to expectations, here the applicant’s laboratory presents preliminary data indicating that antibody-mediated NK cell depletion or genetic absence of NK cells enhanced ICT in mice, suggesting NK cells subvert ICT. Moreover, transfer of NK cells into the tumor itself in mice genetically lacking NK cells restored subversion of ICT. Furthermore, anti-NKG2D also enhanced ICT. Finally, the applicant provides evidence from human tumor databases that a similar process may be occurring in patients. Thus, NK cells subvert ICT and NKG2D appears to be involved in this process. Therefore, the Specific Aims of this proposal are to: 1) Elucidate effector mechanism(s) by which NK cells constrain ICT; 2) Evaluate contribution of NKG2D; and 3) Translate mouse findings to human tumors. Taken together, this proposal will lead to increased insight on the role of NK cells in ICT and will help guide new strategies to modulate NK cells for improved cancer immunotherapy.


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: 2025 ( Subtotal = $3,182,665 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Treatment Research	000	1	9/22/2025	NEW	$3,182,665
														Subtotal = $3,182,665

Grand Total All Awards = $3,182,665

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Natural killer cells subvert immune checkpoint therapy of tumors

Award Number: R01CA303538

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/24/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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