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Lymphoid residency of Tcf-1+ CD8+ T cells during tumor vaccine responses

Award Number: R01AI177345
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/05/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Lymphoid residency of Tcf-1+ CD8+ T cells during tumor vaccine responses - Project Summary Tumor immunotherapies represent the most exciting advance for cancer patients in recent decades. However, only a minor proportion of treated patients experience long-lasting benefits from current tumor immunotherapies. A subset of tumor-specific T lymphocytes carrying features of memory or progenitor T cells has been named “stem-like” T cells. These stem-like T cells are essential to sustain anti-tumor T cell immunity and are the major responder to several current tumor immunotherapies. Thus, a better understanding of these stem-like T cells will greatly facilitate the improvement of current therapies or the development of future tumor immunotherapies. Tissue-resident memory T cells (TRM) are a subset of non-circulating memory T cells initially discovered after acute infections. Recently, we have discovered that stem-like T cells differentiate into tissue-resident T cells inside tumor-draining lymph nodes, which is negatively associated with the response to tumor vaccine. In other words, a large number of stem-like T cells lose migratory capacity and are trapped inside tumor-draining lymph nodes. However, several open questions remain to be addressed regarding this newly discovered feature of stem- like T cells. For example, what is the lineage relationship between this TRM-stem T cell subsets and other T cells inside tumor-draining lymph nodes? Is there a connection between TRM-stem in TDLN and stem-like T cells inside the tumor microenvironment? Whether can we manipulate TRM program of stem-like T cells to boost tumor vaccine? In this application, we will use multiple well-established tumor models to track tumor-specific CD8+ T cell response in the presence and absence of tumor vaccination. We will answer this series of questions focusing on this unique T cell subset, i.e., TRM-stem. Further, our proposal will primarily focus on tumor-draining lymph nodes, which serve as a reservoir for tumor-specific stem-like T cells. Our proposed studies will greatly advance our understanding of stem-like T-cell biology. Importantly, we will establish a new targeting organ (tumor-draining lymph nodes) and a novel target (the lymphoid residency program of stem-like T cells) to boost the efficacy of tumor vaccine.


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 = $441,601 )
2026	2026	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	000	3	12/9/2025	NON-COMPETING CONTINUATION	$441,601
														Subtotal = $441,601

Issue Date FY: 2025 ( Subtotal = $428,354 )
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	000	2	12/6/2024	NON-COMPETING CONTINUATION	$428,354
														Subtotal = $428,354

Issue Date FY: 2024 ( Subtotal = $441,601 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	001	1	9/4/2024	NEW	$44,160
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	000	1	2/5/2024	NEW	$397,441
														Subtotal = $441,601

Grand Total All Awards = $1,311,556

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Lymphoid residency of Tcf-1+ CD8+ T cells during tumor vaccine responses

Award Number: R01AI177345

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/05/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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