Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas

Shah, Shivem B.; Carlson, Christopher R.; Lai, Kristine; Zhong, Zhe; Marsico, Grazia; Lee, Katherine M.; Vélez, Nicole E. Félix; Abeles, Elisabeth B.; Allam, Mayar; Hu, Thomas; Walter, Lauren D.; Martin, Karen E.; Gandhi, Khanjan; Butler, Scott D.; Puri, Rishi; McCleary‐Wheeler, Angela L.; Elemento, Olivier; Takata, Katsuyoshi; Scott, David W.; Fontán, Lorena; Ueno, Hideki; Cosgrove, Benjamin D.; Inghirami, Giorgio; Garcı́a, Andrés J.; Coşkun, Ahmet F.; Koff, Jean L.; Melnick, Ari; Singh, Ankur

doi:10.1038/s41563-023-01495-3

Cited by 18 publications

(9 citation statements)

References 59 publications

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“…Cg-rkdcscid Il2rgtm1Wjl/SzJ mice were used to establish the PDX mouse model. Subsequently, tumours were removed and grown in bioadhesive polyethene glycol hydrogels to establish DLBCL 3D organoids ( 70 , 74 ). Similarly, to further explore whether senolytics are effective in humans, the investigators used human tissue explants (including tumour tissues) by in vitro culture to demonstrate the efficacy of senolytics ( 63 ).…”

Section: Research Model Applications In Senescence-associated Lymphom...mentioning

confidence: 99%

Ageing microenvironment mediates lymphocyte carcinogenesis and lymphoma drug resistance: From mechanisms to clinical therapy (Review)

Zhang,

Chu,

Hou

et al. 2024

Int J Oncol

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Cellular senescence has a complex role in lymphocyte carcinogenesis and drug resistance of lymphomas. Senescent lymphoma cells combine with immunocytes to create an ageing environment that can be reprogrammed with a senescence-associated secretory phenotype, which gradually promotes therapeutic resistance. Certain signalling pathways, such as the NF-κB, Wnt and PI3K/AKT/mTOR pathways, regulate the tumour ageing microenvironment and induce the proliferation and progression of lymphoma cells. Therefore, targeting senescence-related enzymes or their signal transduction pathways may overcome radiotherapy or chemotherapy resistance and enhance the efficacy of relapsed/refractory lymphoma treatments. Mechanisms underlying drug resistance in lymphomas are complex. The ageing microenvironment is a novel factor that contributes to drug resistance in lymphomas. In terms of clinical translation, some senolytics have been used in clinical trials on patients with relapsed or refractory lymphoma. Combining immunotherapy with epigenetic drugs may achieve better therapeutic effects; however, senescent cells exhibit considerable heterogeneity and lymphoma has several subtypes. Extensive research is necessary to achieve the practical application of senolytics in relapsed or refractory lymphomas. This review summarises the mechanisms of senescence-associated drug resistance in lymphoma, as well as emerging strategies using senolytics, to overcome therapeutic resistance in lymphoma.

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Section: Research Model Applications In Senescence-associated Lymphom...mentioning

confidence: 99%

Ageing microenvironment mediates lymphocyte carcinogenesis and lymphoma drug resistance: From mechanisms to clinical therapy (Review)

Zhang,

Chu,

Hou

et al. 2024

Int J Oncol

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“… 279 A B-cell lymphoma in vitro model based on a similar strategy informed the design of a novel combination therapy to attenuate treatment resistance. 280 Hydrogel has also been incorporated into microfluidic devices to assess B cell responses against vaccines. 281 These studies collectively showcased the potential of biomaterials in facilitating B cell immunobiology and vaccine screening by serving as reductionist models for germinal centers or disease tissues.…”

Section: Outlook and Conclusionmentioning

confidence: 99%

Biomaterial engineering strategies for B cell immunity modulations

Zareein,

Mahmoudi,

Jadhav

et al. 2024

Biomater. Sci.

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“…The protumoral TME components that have been widely used to maintain FL B cell survival and proliferation in vitro are CD40L and IL-4, mimicking the interaction with FL-Tfh (14-16), which overexpress both factors within invaded LN. More recently, CD40L has also been shown to be efficient in sustaining the survival and drug resistance of ABC-DLBCL in vitro (17). In addition to Tfh, stromal cells are another key component of lymphoma TME frequently used in in vitro models (18).…”

Section: D Modelsmentioning

confidence: 99%

Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: challenges and opportunities

Brauge,

Dessauge,

Creusat

et al. 2023

Front. Immunol.

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B-cell lymphomas are a group of heterogeneous neoplasms resulting from the clonal expansion of mature B cells arrested at various stages of differentiation. Specifically, two lymphoma subtypes arise from germinal centers (GCs), namely follicular lymphoma (FL) and GC B-cell diffuse large B-cell lymphoma (GCB-DLBCL). In addition to recent advances in describing the genetic landscape of FL and GCB-DLBCL, tumor microenvironment (TME) has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, and late progression/transformation. The lymphoma-supportive niche integrates a dynamic and coordinated network of immune and stromal cells defining microarchitecture and mechanical constraints and regulating tumor cell migration, survival, proliferation, and immune escape. Several questions are still unsolved regarding the interplay between lymphoma B cells and their TME, including the mechanisms supporting these bidirectional interactions, the impact of the kinetic and spatial heterogeneity of the tumor niche on B-cell heterogeneity, and how individual genetic alterations can trigger both B-cell intrinsic and B-cell extrinsic signals driving the reprogramming of non-malignant cells. Finally, it is not clear whether these interactions might promote resistance to treatment or, conversely, offer valuable therapeutic opportunities. A major challenge in addressing these questions is the lack of relevant models integrating tumor cells with specific genetic hits, non-malignant cells with adequate functional properties and organization, extracellular matrix, and biomechanical forces. We propose here an overview of the 3D in vitro models, xenograft approaches, and genetically-engineered mouse models recently developed to study GC B-cell lymphomas with a specific focus on the pros and cons of each strategy in understanding B-cell lymphomagenesis and evaluating new therapeutic strategies.

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Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas

Cited by 18 publications

References 59 publications

Ageing microenvironment mediates lymphocyte carcinogenesis and lymphoma drug resistance: From mechanisms to clinical therapy (Review)

Ageing microenvironment mediates lymphocyte carcinogenesis and lymphoma drug resistance: From mechanisms to clinical therapy (Review)

Biomaterial engineering strategies for B cell immunity modulations

Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: challenges and opportunities

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