Tumor Immune Microenvironment in Lymphoma: Focus on Epigenetics

García-Domínguez, Daniel J.; Hontecillas-Prieto, Lourdes; Palazón‐Carrión, Natalia; Jiménez‐Cortegana, Carlos; Sánchez-Margalet, Vı́ctor; Cruz‐Merino, Luis de la

doi:10.3390/cancers14061469

Cited by 11 publications

(8 citation statements)

References 231 publications

(280 reference statements)

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“…EZH2) and non-coding RNA (e.g. miR-155) ( 94 ). Personalized therapies can be used to target these alterations, for example tazemetostat, an oral EZH2-inhibitor, produces durable responses in the setting of relapsed and refractory follicular lymphoma ( 95 ).…”

Section: Spatial Transcriptomics In Lymphoma: the Futurementioning

confidence: 99%

Location, location, location: mapping the lymphoma tumor microenvironment using spatial transcriptomics

Pickard,

Stephenson,

Mitchell

et al. 2023

Front. Oncol.

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Lymphomas are a heterogenous group of lymphoid neoplasms with a wide variety of clinical presentations. Response to treatment and prognosis differs both between and within lymphoma subtypes. Improved molecular and genetic profiling has increased our understanding of the factors which drive these clinical dynamics. Immune and non-immune cells within the lymphoma tumor microenvironment (TME) can both play a key role in antitumor immune responses and conversely also support lymphoma growth and survival. A deeper understanding of the lymphoma TME would identify key lymphoma and immune cell interactions which could be disrupted for therapeutic benefit. Single cell RNA sequencing studies have provided a more comprehensive description of the TME, however these studies are limited in that they lack spatial context. Spatial transcriptomics provides a comprehensive analysis of gene expression within tissue and is an attractive technique in lymphoma to both disentangle the complex interactions between lymphoma and TME cells and improve understanding of how lymphoma cells evade the host immune response. This article summarizes current spatial transcriptomic technologies and their use in lymphoma research to date. The resulting data has already enriched our knowledge of the mechanisms and clinical impact of an immunosuppressive TME in lymphoma and the accrual of further studies will provide a fundamental step in the march towards personalized medicine.

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Section: Spatial Transcriptomics In Lymphoma: the Futurementioning

confidence: 99%

Location, location, location: mapping the lymphoma tumor microenvironment using spatial transcriptomics

Pickard,

Stephenson,

Mitchell

et al. 2023

Front. Oncol.

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“…Compounds which improve CAR T-cell killing such as decitabine may also serve as supplemental treatments to ensure long-term killing of CAR T-cells in order to avoid exhaustion and subsequent relapse [ 191 , 192 ]. Indeed, multiple early phase clinical trials exist to determine the use of decitabine primed CAR T-cells in their role in treating R/R NHL (clinicaltrial.gov identifiers, NCT04697940, NCT04850560) [ 193 ].…”

Section: Advances In the Treatment Of Pediatric And Adolescent Nhlmentioning

confidence: 99%

Management of Aggressive Non-Hodgkin Lymphomas in the Pediatric, Adolescent, and Young Adult Population: An Adult vs. Pediatric Perspective

Sheikh

Elgehiny²,

Ragoonanan

et al. 2022

Cancers

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Non-Hodgkin lymphoma (NHL) is a broad entity which comprises a number of different types of lymphomatous malignancies. In the pediatric and adolescent population, the type and prognosis of NHL varies by age and gender. In comparison to adults, pediatric and adolescent patients generally have better outcomes following treatment for primary NHL. However, relapsed/refractory (R/R) disease is associated with poorer outcomes in many types of NHL such as diffuse large B cell lymphoma and Burkitt lymphoma. Newer therapies have been approved in the use of primary NHL in the pediatric and adolescent population such as Rituximab and other therapies such as chimeric antigen receptor T-cell (CAR T-cell) therapy are under investigation for the treatment of R/R NHL. In this review, we feature the characteristics, diagnosis, and treatments of the most common NHLs in the pediatric and adolescent population and also highlight the differences that exist between pediatric and adult disease. We then detail the areas of treatment advances such as immunotherapy with CAR T-cells, brentuximab vedotin, and blinatumomab as well as cell cycle inhibitors and describe areas where further research is needed. The aim of this review is to juxtapose established research regarding pediatric and adolescent NHL with recent advancements as well as highlight treatment gaps where more investigation is needed.

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“…Lymphoproliferative diseases comprise a diverse and heterogeneous group of malignancies ( 1 ). Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype, accounting 30%-40% of lymphoid malignancies ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma

Hontecillas-Prieto,

García-Domínguez,

Palazón-Carrión

et al. 2024

Front. Immunol.

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BackgroundDiffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients.Methods78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients.ResultsOur results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients.ConclusionCD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

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Tumor Immune Microenvironment in Lymphoma: Focus on Epigenetics

Cited by 11 publications

References 231 publications

Location, location, location: mapping the lymphoma tumor microenvironment using spatial transcriptomics

Location, location, location: mapping the lymphoma tumor microenvironment using spatial transcriptomics

Management of Aggressive Non-Hodgkin Lymphomas in the Pediatric, Adolescent, and Young Adult Population: An Adult vs. Pediatric Perspective

CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma

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