ArticleBlood2021
Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase Ib Multi-Cohort Trial of MK-3475 (Pembrolizumab) in Subjects With Hematologic Malignancies
A Phase 2 Study of Pembrolizumab in Patients With Histiocyte/Dendritic Cell Neoplasms and Biologically Selected Subtypes of Relapsed/Refractory Aggressive Lymphomas
Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
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- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- Integrating new and "old" cellular therapies in the evolving landscape of relapsed or refractory large B-cell lymphoma.Frontiers in oncology · 2026Review
- A cellular and spatial atlas of TP53-associated tissue remodeling defines a multicellular tumor ecosystem in lung adenocarcinoma.Nature cancer · 2025Article
- Combining CAR T-Cell Therapy and Nivolumab to Overcome Immune Resistance in THRLBCL: A Case Report.International journal of molecular sciences · 2025Article
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- Immunoprofiling at an Institutional Scale Reveals That High Numbers of Intratumoral CD8JCO precision oncology · 2025Article
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- A Case of Atraumatic Splenic Rupture Due to T-Cell/Histiocyte-Rich Large B-Cell Lymphoma and a Potential Role for Massive Transfusion Protocol.Case reports in surgery · 2025Article
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- CD19-directed CART therapy for T-cell/histiocyte-rich large B-cell lymphoma.Blood advances · 2024Article
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- Spatial iTME analysis of KRAS mutant NSCLC and immunotherapy outcome.NPJ precision oncology · 2024Article
- The spectrum of nodular lymphocyte predominant Hodgkin lymphoma: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.Virchows Archiv : an international journal of pathology · 2023Review
- Spatially aware deep learning reveals tumor heterogeneity patterns that encode distinct kidney cancer states.Cell reports. Medicine · 2023Article
- Diffuse large B-cell lymphomas have spatially defined, tumor immune microenvironments revealed by high-parameter imaging.Blood advances · 2023Article
- Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions.Blood advances · 2023Article
- Whole-Slide Imaging, Mutual Information Registration for Multiplex Immunohistochemistry and Immunofluorescence.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Tumor microenvironment contribution to checkpoint blockade therapy: lessons learned from Hodgkin lymphoma.Blood · 2023Article
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Authors and funding
31 authors at 7 institutions in 3 countries.
Funding
Abstract
T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) characterized by rare malignant B cells within a robust but ineffective immune cell infiltrate. The mechanistic basis of immune escape in TCRLBCL is poorly defined and not targeted therapeutically. We performed a genetic and quantitative spatial analysis of the PD-1/PD-L1 pathway in a multi-institutional cohort of TCRLBCLs and found that malignant B cells harbored PD-L1/PD-L2 copy gain or amplification in 64% of cases, which was associated with increased PD-L1 expression (P = .0111). By directed and unsupervised spatial analyses of multiparametric cell phenotypic data within the tumor microenvironment, we found that TCRLBCL is characterized by tumor-immune "neighborhoods" in which malignant B cells are surrounded by exceptionally high numbers of PD-L1-expressing TAMs and PD-1+ T cells. Furthermore, unbiased clustering of spatially resolved immune signatures distinguished TCRLBCL from related subtypes of B-cell lymphoma, including classic Hodgkin lymphoma (cHL) and DLBCL-NOS. Finally, we observed clinical responses to PD-1 blockade in 3 of 5 patients with relapsed/refractory TCRLBCL who were enrolled in clinical trials for refractory hematologic malignancies (NCT03316573; NCT01953692), including 2 complete responses and 1 partial response. Taken together, these data implicate PD-1 signaling as an immune escape pathway in TCRLBCL and also support the potential utility of spatially resolved immune signatures to aid the diagnostic classification and immunotherapeutic prioritization of diverse tumor types.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.