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Study of Anti-Tumor Immunity and Tissue Resident Memory Cell Development by NKG2D and Ribosomal Protein S6 Signaling in T cells

Award Number: R01CA250514
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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In the field of tumor immunology, while the generation and maintenance of anti-tumor CD8 T cell memory responses are considered crucial for the long-term host survival, the basic tenets of memory formation remain to be established. We propose to study and manipulate the CD8 T cell NKG2D/DAP10 ¿ ribosomal protein S6 (rpS6) pathway as a means to generate durable and protective anti-tumor immunity. The scientific premise of this study is derived from our work demonstrating that NKG2D signaling provides CD8 T cells with pro-memory signals. We hypothesize that NKG2D, through finely tuned DAP10PI3K/Grb2 signaling (as NKG2D cannot signal by itself, instead uses DAP10PI3K/Grb2 as signaling adaptor), activates rpS6 resulting in the development of functionally capable CD8 memory T cells. This proposal will define the underlying players required for rpS6 phosphorylation downstream of NKG2D/DAP10 and its implications in the development of immunological memory against tumors including TRM cells. Here we will conduct proof-of-concept tests utilizing human and mouse tumors, with the intention of preparing for a clinical trial. SA1: TO DETERMINE THE MOLECULAR CONTRIBUTORS OF NKG2D-DAP10 INDUCED PHOSPHORYLATION OF rpS6 SA2. TO DETERMINE THE ROLE OF NKG2D/DAP10PI3K/GRB2 IN THE DEVELOPMENT OF TRADITIONAL MEMORY RESPONSES AND SKIN TRM CELLS AGAINST MELANOMA. SA3. TO EVALUATE THE THERAPEUTIC POTENTIAL OF MANIPULATING THE DAP10/rpS6 PATHWAY IN CD8 T CELLS


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: 2024 ( Subtotal = $357,915 )
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	000	6	2/8/2024	NON-COMPETING CONTINUATION	$339,076
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	001	6	4/17/2024	NON-COMPETING CONTINUATION	$18,839
														Subtotal = $357,915

Issue Date FY: 2023 ( Subtotal = $368,061 )
2023	2023	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	001	5	2/27/2023	NON-COMPETING CONTINUATION	$369,216
2023	2020	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Cancer Cause and Prevention Research	000	1	2/2/2023	NEW	-$1,155
														Subtotal = $368,061

Issue Date FY: 2022 ( Subtotal = $370,371 )
2022	2022	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	002	4	1/25/2022	NON-COMPETING CONTINUATION	$339,075
2022	2022	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	003	4	6/13/2022	NON-COMPETING CONTINUATION	$30,141
2022	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	001	3	11/23/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$28,931
2022	2020	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Cancer Cause and Prevention Research	000	1	11/23/2021	NEW	-$28,931
2022	2020	LOYOLA UNIVERSITY OF CHICAGO	2160 S 1ST AVE	MAYWOOD	IL	60153	COOK	USA	Cancer Cause and Prevention Research	004	1	9/26/2022	NEW	$1,155
														Subtotal = $370,371

Issue Date FY: 2021 ( Subtotal = $344,757 )
2021	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Cause and Prevention Research	002	3	9/15/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$344,757
2021	2021	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Cancer Cause and Prevention Research	000	2	3/3/2021	NON-COMPETING CONTINUATION	$344,757
2021	2021	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Cancer Cause and Prevention Research	001	2	9/14/2021	NON-COMPETING CONTINUATION	-$344,757
														Subtotal = $344,757

Issue Date FY: 2020 ( Subtotal = $343,320 )
2020	2020	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Cancer Cause and Prevention Research	000	1	3/5/2020	NEW	$343,320
														Subtotal = $343,320

Grand Total All Awards = $1,784,424

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Study of Anti-Tumor Immunity and Tissue Resident Memory Cell Development by NKG2D and Ribosomal Protein S6 Signaling in T cells

Award Number: R01CA250514

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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