Emerging Landscape of Immunotherapy for Primary Central Nervous System Lymphoma

Alcantara, Marion; Fuentealba, Jaime; Soussain, Carole

doi:10.3390/cancers13205061

Cited by 12 publications

(4 citation statements)

References 105 publications

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“…96,97 The current status of immunotherapy in PCNSL is nicely reviewed here. 98 Responses to chemotherapy are poor in the relapsed setting and toxicities are high, indicating that such therapies should only be offered after careful discussion of goals of care and consideration of palliative care or hospice therapy alone. 87…”

Section: Surveillance Postremission Therapymentioning

confidence: 99%

Diagnostic, Pathologic, and Therapeutic Considerations for Primary CNS Lymphoma

D'Angelo

2024

JCO Oncol Pract

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Primary CNS lymphoma (PCNSL) is a rare lymphoma representing 3% of CNS malignancies. The diagnosis is complicated by the unique risks associated with brain biopsy, and the treatment is similarly complicated by the restriction of effective therapeutics able to cross the blood-brain barrier. Currently, the majority of individuals diagnosed with this disease are immunocompetent although immune deficiency related to HIV or immunosuppressive therapy remains an important risk factor. Improvements in both frontline therapy and consolidation options, including the use of hematopoietic stem-cell transplantation, have translated to improved survival. Unfortunately, patients experiencing relapsed or refractory disease often fare poorly. Here, we review key clinical, pathologic, and therapeutic aspects of PCNSL and highlight challenging clinical scenarios that may be encountered by the treating oncologist.

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Section: Surveillance Postremission Therapymentioning

confidence: 99%

Diagnostic, Pathologic, and Therapeutic Considerations for Primary CNS Lymphoma

D'Angelo

2024

JCO Oncol Pract

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“…Indeed, the histogenetic origin of the tumor cells is still debatable, as the CNS is known to not harbor lymphatic vessels or lymph nodes [13]. Interestingly, recent studies showed the presence of lymphatic vessels, parallel to dural venous sinuses, in the meninges of mammals [14]. Moreover, there is growing evidence about the existence of a ''glymphatic system,'' which uses periarterial spaces and constantly clears interstitial fluid into the cerebrospinal fluid through the brain parenchyma [14,15].…”

Section: Pathophysiology and Histogenetic Origin Of Primary Central N...mentioning

confidence: 99%

Pathology and new insights in central nervous system lymphomas

Lebrun

Allard-Demoustiez

Salmon

2023

Current Opinion in Oncology

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Purpose of review Primary central nervous system lymphoma (PCNSL) is a rare central nervous system (CNS) malignancy, which represents a heterogenous group of tumors. Among PCNSL, diffuse large B-cell lymphoma of the CNS (CNS-DLBCL) represents the most common tumor type. Multiomics studies have recently revealed the complex genomic landscape of these rare diseases. These findings lead to a potential new molecular and epigenetic classification. Recent findings Our review is focused on CNS-DLBCL in immunocompetent patients. CNS-DLBCL are derived from self-reactive/polyreactive precursor cells. An early molecular event such as MYD88 mutation leads to escape elimination of precursor cells, which, by a dysregulated GC reaction, acquire auto-/polyreactivity of the B-cell tumoral cells for antigens physiologically expressed in the CNS. Most of CNS-DLBCL tumor cells harbor a non-GCB, ABC-like immunophenotype associated with a late GC (exit) B-cells genotype by gene expression profiling. Various mechanisms of genetic alterations are involved in the pathogenesis of PCNSL, including point mutations [nonsomatic hypermutation (SHM), aberrant SHM (aSHM)], SHM/aSHM, chromosome copy gains or losses, and DNA hypermethylation. Constitutive NFκB activation plays a key role in lymphoma cell proliferation and survival by dysregulation of toll-like receptor (mutations of CARD11 and MYD88), BCR (CD79B), JAK-STAT, and NFκB signaling pathways. Summary Multiomics approaches have succeeded to substantially improve the understanding of the pathogenesis, as well as the molecular and epigenetic events in PCNSL. Challenges remain due to the obvious heterogeneity of CNS-DLBCL, and improvement is needed for their classification.

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“…Pathologically, more than 95% of PCNSL cases are diffuse large B cell lymphoma [ 120 , 121 ]. Gene expression analysis confirmed that non-germinal center B-cell (GCB) is the most common phenotype in PCNSL patients [ 121 – 124 ]. PCNSL cases often carry mutations that lead to activation of the NF-κB pathway, such as activating mutations in MYD88, CDKN2A, TNFAIP3 and CD79 B , suggesting that activation of the NF-κB pathway is a key driver of lymphangiogenesis in PCNSL[ 123 , 125 – 136 ].…”

Section: Primary Central Nervous System Lymphomamentioning

confidence: 99%

Extranodal lymphoma: pathogenesis, diagnosis and treatment

Yang,

Xun,

et al. 2023

Mol Biomed

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Approximately 30% of lymphomas occur outside the lymph nodes, spleen, or bone marrow, and the incidence of extranodal lymphoma has been rising in the past decade. While traditional chemotherapy and radiation therapy can improve survival outcomes for certain patients, the prognosis for extranodal lymphoma patients remains unsatisfactory. Extranodal lymphomas in different anatomical sites often have distinct cellular origins, pathogenic mechanisms, and clinical manifestations, significantly influencing their diagnosis and treatment. Therefore, it is necessary to provide a comprehensive summary of the pathogenesis, diagnosis, and treatment progress of extranodal lymphoma overall and specifically for different anatomical sites. This review summarizes the current progress in the common key signaling pathways in the development of extranodal lymphomas and intervention therapy. Furthermore, it provides insights into the pathogenesis, diagnosis, and treatment strategies of common extranodal lymphomas, including gastric mucosa-associated lymphoid tissue (MALT) lymphoma, mycosis fungoides (MF), natural killer/T-cell lymphoma (nasal type, NKTCL-NT), and primary central nervous system lymphoma (PCNSL). Additionally, as PCNSL is one of the extranodal lymphomas with the worst prognosis, this review specifically summarizes prognostic indicators and discusses the challenges and opportunities related to its clinical applications. The aim of this review is to assist clinical physicians and researchers in understanding the current status of extranodal lymphomas, enabling them to make informed clinical decisions that contribute to improving patient prognosis.

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Emerging Landscape of Immunotherapy for Primary Central Nervous System Lymphoma

Cited by 12 publications

References 105 publications

Diagnostic, Pathologic, and Therapeutic Considerations for Primary CNS Lymphoma

Diagnostic, Pathologic, and Therapeutic Considerations for Primary CNS Lymphoma

Pathology and new insights in central nervous system lymphomas

Extranodal lymphoma: pathogenesis, diagnosis and treatment

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