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Dissecting temporal and spatial dynamics of immunotherapy resistance

Award Number: K23DE029811
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Dissecting temporal and spatial dynamics of immunotherapy resistance - PROJECT SUMMARY Immune checkpoint inhibitors (ICI) are now used as first line therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), yet, only one out of six patients respond. How the composition and spatial organization of the tumor immune microenvironment relates to ICI efficacy in HNSCC is currently poorly understood. What is known, is that cancers are dynamic, evolving temporally and spatially in response to therapeutic pressures, with building support suggesting that on treatment assessment is more predictive of ICI response than assessment of pre-treatment tissue. In this proposal we will apply innovative single cell sequencing and imaging approaches to answer a critical question impeding progress in head and neck cancer care: how the spatial and temporal evolution of tumor and immune cells impacts ICI resistance. Aim 1 will distinguish tumor cell programs that associate with ICI resistance in primary tissue and serially measure alterations in these genes in circulating tumor cells. Aim 2 will define how T and B cell subpopulations and spatial architecture change with ICI initiation and how alterations relate to ICI resistance. Completion of these mentored aims will set the stage for the long term goal of developing improved predictive biomarkers of ICI response and identifying new targets for combinatorial therapies. This career development proposal presents a five-year plan to both accomplish the outlined scientific aims as well as a detailed training program to ensure the candidate’s transition to research independence. The candidate is an Instructor in Otolaryngology-Head and Neck Surgery at Harvard Medical School, Massachusetts Eye and Ear and Massachusetts General Hospital. The training aims, which include hand on experience, coursework and seminars focused on immunogenomics, build on the candidate’s previous research experience in cancer genomics and clinical experience as a head and neck cancer surgeon. Mentorship will be provided by thought leaders in single cell imaging and sequencing, bioinformatics, biomarker science, and cancer immunology including the primary mentorship team of Dr. Shannon Stott, PhD, Keith Flaherty, MD and Nir Hacohen, PhD at Massachusetts General Hospital Cancer Center.


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 = $0 )
2026	2025	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	5	1/23/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $173,772 )
2025	2025	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	5	3/20/2025	NON-COMPETING CONTINUATION	$173,772
														Subtotal = $173,772

Issue Date FY: 2024 ( Subtotal = $173,772 )
2024	2024	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	4	3/21/2024	NON-COMPETING CONTINUATION	$173,772
														Subtotal = $173,772

Issue Date FY: 2023 ( Subtotal = $173,772 )
2023	2023	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	3	3/16/2023	NON-COMPETING CONTINUATION	$173,772
														Subtotal = $173,772

Issue Date FY: 2022 ( Subtotal = $173,772 )
2022	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	001	2	3/3/2022	NON-COMPETING CONTINUATION	$173,772
2022	2021	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	1	10/21/2021	NEW	$0
														Subtotal = $173,772

Issue Date FY: 2021 ( Subtotal = $173,772 )
2021	2021	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	1	3/18/2021	NEW	$173,772
														Subtotal = $173,772

Grand Total All Awards = $868,860

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Dissecting temporal and spatial dynamics of immunotherapy resistance

Award Number: K23DE029811

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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