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Chemokine-mediated antigen-specific T cell responses and immunotherapies to treat head and neck cancer

Award Number: R01DE029524
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Human papillomaviruses (HPVs) are causally linked to 5% of all human cancers, including nearly all cervical cancers and ~25% of head and neck squamous cell carcinomas (HNSCCs), largely driving an ongoing epidemic increase of HPV-positive (HPV+) HNSCCs over recent decades. However, little is known about the mechanisms of disease progression driven by HPV, particularly in the context of host immunity. Based on our preliminary findings, we will study the mechanism by which the chemokine CXCL14 suppresses HNSCC growth, and test if CXCL14 serves as a useful immunomodulatory target for novel immunotherapies to treat HPV+ HNSCC. Recently, we have revealed that restoring the suppressed expression of CXCL14 in HPV+ HNSCC cells greatly suppressed tumor growth in immunocompetent syngeneic mice through upregulation of MHC-I antigen presentation and antigen-specific CD8+ T cells responses. Based on our findings, we hypothesize that CXCL14 induces antitumor immune responses that suppress HPV+ HNSCC by enhancing antigen presentation and eliciting CD8+ T cell responses, and thus CXCL14 is a potential novel immunotherapeutic agent. To test our hypothesis, we will 1) Define the mechanisms by which CXCL14 upregulates MHC-I antigen presentation to mediate tumor suppression; 2) Define the mechanisms by which CXCL14 induces CD8+ T cell infiltration/activation and tumor suppression; and 3) Test CXCL14-based immunotherapies that induce antitumor immunity and clear HPV+ HNSCC. Our study will provide new mechanistic understanding of antitumor immune defenses in HPV+ HNSCC and may lead to a novel immunotherapy for HNSCC, particularly for the non- responders in current immunotherapies.


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 = $590,633 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Oral Diseases and Disorders Research	000	5	4/16/2024	NON-COMPETING CONTINUATION	$590,633
														Subtotal = $590,633

Issue Date FY: 2023 ( Subtotal = $656,258 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Oral Diseases and Disorders Research	000	4	4/5/2023	NON-COMPETING CONTINUATION	$656,258
														Subtotal = $656,258

Issue Date FY: 2022 ( Subtotal = $641,281 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Oral Diseases and Disorders Research	000	3	4/27/2022	NON-COMPETING CONTINUATION	$641,281
														Subtotal = $641,281

Issue Date FY: 2021 ( Subtotal = $657,132 )
2021	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Oral Diseases and Disorders Research	000	2	4/21/2021	NON-COMPETING CONTINUATION	$657,132
														Subtotal = $657,132

Issue Date FY: 2020 ( Subtotal = $626,815 )
2020	2020	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Oral Diseases and Disorders Research	000	1	6/9/2020	NEW	$626,815
														Subtotal = $626,815

Grand Total All Awards = $3,172,119

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Chemokine-mediated antigen-specific T cell responses and immunotherapies to treat head and neck cancer

Award Number: R01DE029524

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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