Multi-omic profiling of follicular lymphoma reveals changes in tissue architecture and enhanced stromal remodeling in high-risk patients.

in Cancer cell by Andrea J Radtke, Ekaterina Postovalova, Arina Varlamova, Alexander Bagaev, Maria Sorokina, Olga Kudryashova, Mark Meerson, Margarita Polyakova, Ilia Galkin, Viktor Svekolkin, Sergey Isaev, Daniil Wiebe, Anna Sharun, Alexander Sarachakov, Grigory Perelman, Yaroslav Lozinsky, Ziv Yaniv, Bradley C Lowekamp, Emily Speranza, Li Yao, Stefania Pittaluga, Arthur L Shaffer, Danny Jonigk, James D Phelan, Theresa Davies-Hill, Da Wei Huang, Pavel Ovcharov, Krystle Nomie, Ekaterina Nuzhdina, Nikita Kotlov, Ravshan Ataullakhanov, Nathan Fowler, Michael Kelly, Jagan Muppidi, Jeremy L Davis, Jonathan M Hernandez, Wyndham H Wilson, Elaine S Jaffe, Louis M Staudt, Mark Roschewski, Ronald N Germain

TLDR

  • The study looked at how the cells in a type of cancer called follicular lymphoma (FL) work and how they interact with the environment around them. The study found that certain changes in the cells and their environment were more likely to happen in people who experienced early relapse, which is when the cancer comes back. This could help doctors predict which patients are at the highest risk of relapse and develop better treatments for them.

Abstract

Follicular lymphoma (FL) is a generally incurable malignancy that evolves from developmentally blocked germinal center (GC) B cells. To promote survival and immune escape, tumor B cells undergo significant genetic changes and extensively remodel the lymphoid microenvironment. Dynamic interactions between tumor B cells and the tumor microenvironment (TME) are hypothesized to contribute to the broad spectrum of clinical behaviors observed among FL patients. Despite the urgent need, existing clinical tools do not reliably predict disease behavior. Using a multi-modal strategy, we examined cell-intrinsic and -extrinsic factors governing progression and therapeutic outcomes in FL patients enrolled onto a prospective clinical trial. By leveraging the strengths of each platform, we identify several tumor-specific features and microenvironmental patterns enriched in individuals who experience early relapse, the most high-risk FL patients. These features include stromal desmoplasia and changes to the follicular growth pattern present 20 months before first progression and first relapse.

Overview

  • The study focuses on follicular lymphoma (FL), a generally incurable malignancy that evolves from developmentally blocked germinal center (GC) B cells. The hypothesis being tested is that dynamic interactions between tumor B cells and the tumor microenvironment (TME) contribute to the broad spectrum of clinical behaviors observed among FL patients. The methodology used for the experiment includes a multi-modal strategy that examines cell-intrinsic and -extrinsic factors governing progression and therapeutic outcomes in FL patients enrolled onto a prospective clinical trial. The primary objective of the study is to identify tumor-specific features and microenvironmental patterns enriched in individuals who experience early relapse, the most high-risk FL patients.

Comparative Analysis & Findings

  • The study compares outcomes observed under different experimental conditions or interventions detailed in the study. The results show that stromal desmoplasia and changes to the follicular growth pattern present 20 months before first progression and first relapse are enriched in individuals who experience early relapse, the most high-risk FL patients. These findings suggest that dynamic interactions between tumor B cells and the TME contribute to the broad spectrum of clinical behaviors observed among FL patients and that these interactions may be used to predict disease behavior.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice. The identification of tumor-specific features and microenvironmental patterns enriched in individuals who experience early relapse may lead to the development of more accurate clinical tools for predicting disease behavior. The study also highlights the importance of dynamic interactions between tumor B cells and the TME in the development of FL and suggests that these interactions may be targeted for therapeutic purposes. Future research directions could include further exploration of the role of the TME in FL and the development of novel therapies that target these interactions.
Read Full Article