Study underscores the value of a multi-omic approach to examine cell-intrinsic and -extrinsic factors governing progression and therapeutic outcomes in follicular lymphoma patients in a prospective clinical trial

BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, today announced the publication of the manuscript, “Multi-omic Profiling of Follicular Lymphoma Reveals Changes in Tissue Architecture and Enhanced Stromal Remodeling in High-Risk Patients” in Cancer Cell, a premier peer-reviewed scientific journal that publishes high-impact results in cancer research and oncology.

Follicular lymphoma (FL), an often incurable malignancy, stems from developmentally blocked germinal center B cells. Throughout its progression, FL tumor B cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment to promote survival and immune evasion. The dynamic interaction between tumor B cells and the tumor microenvironment are thought to influence the diverse clinical behaviors observed among FL patients, ranging from an indolent disease to a more aggressive clinical course characterized by progression after therapy, histologic transformation, and premature death from lymphoma. Despite the urgent need, current clinical tools inadequately predict disease behavior, underscoring the necessity for risk stratification methods, particularly for early relapsers.

The study, led by researchers at the National Institute of Allergy and Infectious Diseases and National Cancer Institute in collaboration with BostonGene, employed a multi-modal approach to comprehensively examine cell-intrinsic and -extrinsic factors governing disease progression and therapeutic outcomes in FL patients enrolled in a prospective clinical trial. Utilizing BostonGene’s advanced end-to-end bioinformatics and proprietary software, the researchers identified several tumor-specific features and microenvironmental patterns associated with early relapse, the most high-risk subgroup of FL patients.

The research's key findings included identifying unique histological patterns such as stromal desmoplasia and follicular growth pattern alterations observed before first progression and relapse in FL patients. Additional results provide a comprehensive characterization of the genomic and transcriptomic landscapes of tumor B cells, uncovering diverse genetic lesions and alterations in pathways associated with immune escape, apoptosis resistance, and extracellular matrix remodeling. Utilizing single-cell resolution profiling, the research revealed distinct populations of B cells, T cells, myeloid cells, and stromal cells within FL lymph nodes, shedding light on their spatial distribution within the tumor microenvironment. Moreover, the researchers established a correlation between gene signatures linked to poor prognosis and extracellular matrix remodeling with cellular communities identified in FL lymph nodes, offering potential therapeutic targets for high-risk patients.

"The insights garnered from this study signal a pivotal moment in refining treatment strategies for follicular lymphoma patients," said Nathan Fowler, MD, Chief Medical Officer at BostonGene. "By unraveling the intricate molecular and cellular dynamics steering disease progression, we advance toward implementing precision medicine paradigms that can reshape the standard of care.”

Research reported in this press release was supported by the National Institute of Allergy and Infectious Diseases and National Cancer Institute, parts of the National Institutes of Health, under award numbers Z01 AI000545, ZIA BC011914, Z01 SC004024, and Z01 BC011006. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About BostonGene Corporation

BostonGene has a mission to provide transformative, AI-integrated molecular analytics and biomarker discovery for precision matching of therapies to improve the lives of patients living with cancer and other immune-related diseases. BostonGene’s concierge-service model provides customized client solutions using a multi-omic approach prioritized for real-world impact to optimize standard-of-care therapies, accelerate research and provide cost-effective, measurable data-driven results. BostonGene’s tests reveal key drivers of each patient’s unique disease profile, including an in-depth profile of the immune microenvironment, actionable mutations, biomarkers of response to diverse therapies, and recommended therapies. Through these comprehensive analyses, BostonGene’s tests generate a personalized roadmap for therapeutic decision-making for each patient. For more information, visit BostonGene at http://www.BostonGene.com.

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"By unraveling the intricate molecular and cellular dynamics steering disease progression, we advance toward implementing precision medicine paradigms that can reshape the standard of care.”