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Comprehensive Profiling of Tumor and Tumor Immunity for Developing Personalized Interventions for T-cell Lymphomas

Award Number: K99CA307609
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Comprehensive Profiling of Tumor and Tumor Immunity for Developing Personalized Interventions for T-cell Lymphomas - Project Summary/Abstract T-cell lymphoma (TCL) is a malignancy with high relapse rates and poor prognosis, underscoring the pressing need for accurate disease monitoring systems and a more profound understanding of TCL biology to identify patients requiring additional treatments and optimize the application of novel therapies. Prior studies have demonstrated the efficacy of targeted sequencing for ultra-sensitive ctDNA detection (CAPP-Seq) in B-cell lymphoma (BCL) for predicting clinical outcomes. In Aim1, I aim to build on this success by developing a comprehensive approach for disease monitoring, prediction of onset, and clonal evolution assessment in TCL by integrating cutting-edge methods for analyzing viral genomes, immune receptors, and CNVs in cfDNA. I have contributed to the development and refinement of these methods. The tumor microenvironment (TME) plays a pivotal role in TCL progression and response to therapy, with immune escape representing a critical milestone. Current TME profiling approaches rely on invasive tumor biopsies, as not all TME immune cells are found in circulation. However, analysis of tumor tissues provides only a limited snapshot of the disease due to their restricted region of analysis. Recently, we developed EPIC-Seq to infer gene expression from epigenetic changes in cfDNA and RARE-Seq to profile cfRNA expression. In Aim 2, I will leverage EPIC-Seq and RARE-Seq to comprehensively analyze systemic immune dynamics and use spatial analysis of tumor tissues to precisely explore interactions between TME immune cells and tumor T cells, ultimately identifying key immunological factors driving TCL progression. Given the rarity of TCL, preclinical models are essential for evaluating the efficacy of new therapies, including immunotherapy. Building on the success of the lab’s development of patient-derived organoid (PDO) models for follicular lymphoma that replicate the TME, I aim to create PDO models specifically for TCL in Aim 3. Additionally, I will develop a comprehensive atlas of PDOs for various cancer types and organs, incorporating cfDNA from the culture medium and cell composition data from single-cell analysis. This atlas will provide ground truth data on the quantity and epigenetic changes of cfDNA released by different cell types and states, enabling non-invasive tumor and immune monitoring for PDOs and improving the interpretation of plasma cfDNA analysis. The overarching objective is to develop personalized therapies for TCL by achieving a comprehensive understanding of its biology and establishing advanced tumor monitoring systems. To accomplish this, I will integrate multimodal analysis of plasma cfDNA and cfRNA, spatial analysis of tumor tissues, and the development of PDOs tailored for TCL. Furthermore, the creation of a PDO atlas will refine methods for interpreting cfDNA from both PDOs and plasma, enabling precise and accurate tumor and immune monitoring not only for TCL but also for various other cancer types through cfDNA analysis.


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 = $137,266 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cancer Research Manpower	000	1	6/12/2026	NEW	$137,266
														Subtotal = $137,266

Grand Total All Awards = $137,266

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Comprehensive Profiling of Tumor and Tumor Immunity for Developing Personalized Interventions for T-cell Lymphomas

Award Number: K99CA307609

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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