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Published on: February 12, 2022
Integrative Multiomics and Single-Cell Profiling Identify TNFRSF1A+ Macrophages as a Prognostic and Therapeutic
Wenxian Yin1,2,3, Xingyue Wang3, Zhuo Chen4
1Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Computational and Structural Biotechnology Journal
|June 3, 2026
Summary
Tumor-associated macrophages expressing TNFRSF1A drive diffuse large B-cell lymphoma (DLBCL) resistance. Targeting the TNFRSF1A/NF-κB/BAFF pathway with curcumin may overcome R-CHOP resistance in DLBCL.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- The tumor microenvironment is crucial for therapeutic resistance in diffuse large B-cell lymphoma (DLBCL).
- Actionable immune cell targets for overcoming resistance in DLBCL are not well-defined.
Purpose of the Study:
- To identify key immune cell targets within the tumor microenvironment that contribute to R-CHOP resistance in DLBCL.
- To elucidate the mechanisms by which these targets promote lymphoma progression and immunosuppression.
- To explore potential therapeutic strategies for targeting these identified vulnerabilities.
Main Methods:
- Integrative multiomics profiling to identify prognostic determinants.
- Ligand-receptor network analysis and in silico perturbation for mechanistic investigation.
- Pharmacogenomic screening and molecular dynamics simulations to identify therapeutic modulators.
- Experimental validation using siRNA knockdown and coculture assays.
- Development and validation of a risk model based on TAM transcriptional signatures.
Main Results:
- Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) was identified as a key prognostic marker associated with R-CHOP resistance, specifically expressed on tumor-associated macrophages (TAMs).
- TNFRSF1A+ TAMs create a pro-oncogenic and immunosuppressive niche by promoting NF-κB-dependent BAFF secretion and immune checkpoint ligand expression.
- Disruption of the TNFRSF1A/NF-κB/BAFF axis in TAMs abrogated their supportive function for lymphoma cells.
- Curcumin was identified as a potential modulator of TNFRSF1A signaling.
- A novel risk model based on TNFRSF1A+ TAM signature showed strong predictive accuracy for patient outcomes.
Conclusions:
- TNFRSF1A+ TAMs play a significant role in driving DLBCL progression and therapeutic resistance.
- The TNFRSF1A/NF-κB/BAFF axis represents a critical vulnerability within the DLBCL tumor microenvironment.
- Curcumin emerges as a promising therapeutic agent to disrupt this supportive microenvironment and potentially overcome R-CHOP resistance in DLBCL.
