Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities

Liu, Yingyue; Zhou, Xiangxiang; Wang, Xin

doi:10.1186/s13045-021-01134-x

Cited by 64 publications

(50 citation statements)

References 169 publications

(149 reference statements)

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“…Targeting the TME components which play important roles in various processes of B-cell lymphoma could also provide novel insights into the precise treatment of PCNSL. 109 Considering that it is unlikely for a novel agent to cure such a PD as PCNSL, different polychemotherapy combinations of several novel and traditional therapies should be investigated further.…”

Section: Discussionmentioning

confidence: 99%

Novel insights into the biomarkers and therapies for primary central nervous system lymphoma

2022

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Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive extranodal type of non-Hodgkin lymphoma. After the introduction and widespread use of high-dose-methotrexate (HD-MTX)-based polychemotherapy, treatment responses of PCNSL have been improved. However, long-term prognosis for patients who have failed first-line therapy and relapsed remains poor. Less invasive diagnostic markers, including the circulating tumor DNAs (ctDNAs), microRNAs, metabolomic markers, and other novel biomarkers, such as a proliferation inducing ligand (APRIL) and B-cell activating factor of the TNF family (BAFF), have shown potential to distinguish PCNSL at an early stage, and some of them are related with prognosis to a certain extent. Recent insights into novel therapies, including Bruton tyrosine kinase (BTK) inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, PI3K/mTOR inhibitors, and chimeric antigen receptor (CAR) T cells, have revealed encouraging efficacy in treatment response, whereas the duration of response and long-term survival of patients with relapsed or refractory PCNSL (r/r PCNSL) need further improvement. In addition, the diagnostic efficiency of novel markers and the antitumor efficacy of novel therapies are needed to be assessed further in larger clinical trials. This review provides an overview of recent research on novel diagnostic markers and therapeutic strategies for PCNSL.

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Section: Discussionmentioning

confidence: 99%

Novel insights into the biomarkers and therapies for primary central nervous system lymphoma

2022

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“…In addition, consistent with TGFBI function as an extracellular matrix protein involved in mediating cellular interaction, as well as migration, proliferation, apoptosis, and angiogenesis [ 55 ], it is plausible that regulation of its secretion levels may play a major role in reshaping the tumor microenvironment in favor of cancer initiation or progression and treatment resistance. Indeed, throughout the process of oncogenesis, the molecular and cell composition of the microenvironment surrounding both the initial expanding cell clone and the progressively more malignant tumor contributes to cancer onset and progression as much as initial transforming events [ 73 , 74 , 75 , 76 , 77 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development

Manara

Jay

Odongo

et al. 2022

Cancers

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Burkitt lymphoma (BL) is a malignant B cell neoplasm that accounts for almost half of pediatric cancers in sub-Saharan African countries. Although the BL endemic prevalence is attributable to the combination of Epstein–Barr virus (EBV) infection with malaria and environmental carcinogens exposure, such as the food contaminant aflatoxin B1 (AFB1), the molecular determinants underlying the pathogenesis are not fully understood. Consistent with the role of epigenetic mechanisms at the interface between the genome and environment, AFB1 and EBV impact the methylome of respectively leukocytes and B cells specifically. Here, we conducted a thorough investigation of common epigenomic changes following EBV or AFB1 exposure in B cells. Genome-wide DNA methylation profiling identified an EBV–AFB1 common signature within the TGFBI locus, which encodes for a putative tumor suppressor often altered in cancer. Subsequent mechanistic analyses confirmed a DNA-methylation-dependent transcriptional silencing of TGFBI involving the recruitment of DNMT1 methyltransferase that is associated with an activation of the NF-κB pathway. Our results reveal a potential common mechanism of B cell transformation shared by the main risk factors of endemic BL (EBV and AFB1), suggesting a key determinant of disease that could allow the development of more efficient targeted therapeutic strategies.

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“…Based on this concept and these research results, TVEC has been approved by the US FDA for clinical use in patients with advanced malignant melanoma. While intratumoral administration of immunostimulatory agents and noncoding RNAs in solid tumors is a plausible method [ 140 ] and may remodel tumor metabolism and the immune microenvironment [ 141 , 142 ], due to the pathogenesis of AML and MDS, intratumoral vaccination to locally activate tumor-infiltrating DCs may not be widely applicable except in the cases with chloroma as the only presentation.…”

Section: Methods For Vaccine Deliverymentioning

confidence: 99%

Research progress on dendritic cell vaccines in cancer immunotherapy

Sun

Cao

et al. 2022

Exp Hematol Oncol

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Dendritic cell (DC) vaccines induce specific immune responses that can selectively eliminate target cells. In recent years, many studies have been conducted to explore DC vaccination in the treatment of hematological malignancies, including acute myeloid leukemia and myelodysplastic syndromes, as well as other nonleukemia malignancies. There are at least two different strategies that use DCs to promote antitumor immunity: in situ vaccination and canonical vaccination. Monocyte-derived DCs (mo-DCs) and leukemia-derived DCs (DCleu) are the main types of DCs used in vaccines for AML and MDS thus far. Different cancer-related molecules such as peptides, recombinant proteins, apoptotic leukemic cells, whole tumor cells or lysates and DCs/DCleu containing a vaster antigenic repertoire with RNA electroporation, have been used as antigen sources to load DCs. To enhance DC vaccine efficacy, new strategies, such as combination with conventional chemotherapy, monospecific/bispecific antibodies and immune checkpoint-targeting therapies, have been explored. After a decade of trials and tribulations, much progress has been made and much promise has emerged in the field. In this review we summarize the recent advances in DC vaccine immunotherapy for AML/MDS as well as other nonleukemia malignancies.

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Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities

Cited by 64 publications

References 169 publications

Novel insights into the biomarkers and therapies for primary central nervous system lymphoma

Novel insights into the biomarkers and therapies for primary central nervous system lymphoma

Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development

Research progress on dendritic cell vaccines in cancer immunotherapy

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