Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma

Bauer, Vera; Ahmetlić, Fatima; Hömberg, Nadine; Geishauser, Albert; Röcken, Martin; Mocikat, Ralph

doi:10.1016/j.tranon.2021.101170

Cited by 8 publications

(5 citation statements)

References 46 publications

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“…In a study utilizing the λ-MYC mouse model of BL, tumor-promoting Tregs were found to express canonical nTregs markers Helios and NRP-1 and recognized antigens expressed by lymphoma cells ( 71 ). The same group later observed that Tregs progressively upregulated suppressive phenotypic and functional markers during disease progression in this model, including FoxP3, CD25, CTLA-4, PD-1 and IL-10 ( 90 ). Lymphoma-derived Tregs limited responder cell proliferation and IFN-γ production more than WT-derived Tregs, and this suppressive ability was dependent on surface NRP-1, PD-L1 and soluble IL-10.…”

Section: Expression Of Inhibitory Receptors and Immune Checkpoint Blo...mentioning

confidence: 71%

“…The authors further asked whether ICB could affect Tregs. Combination PD-1/CTLA-4 blockade downregulated FoxP3 and CD25 expression on Tregs, indicating functional disruptions ( 90 ). These findings confirmed that Treg changes occurring during lymphoma development could be partially reversed by combination ICB in the λ-MYC model.…”

Section: Expression Of Inhibitory Receptors and Immune Checkpoint Blo...mentioning

confidence: 99%

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Regulatory T cells (Tregs) in lymphoid malignancies and the impact of novel therapies

et al. 2022

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Regulatory T cells (Tregs) are responsible for maintaining immune homeostasis by controlling immune responses. They can be characterized by concomitant expression of FoxP3, CD25 and inhibitory receptors such as PD-1 and CTLA-4. Tregs are key players in preventing autoimmunity and are dysregulated in cancer, where they facilitate tumor immune escape. B-cell lymphoid malignancies are a group of diseases with heterogenous molecular characteristics and clinical course. Treg levels are increased in patients with B-cell lymphoid malignancies and correlate with clinical outcomes. In this review, we discuss studies investigating Treg immunobiology in B-cell lymphoid malignancies, focusing on clinical correlations, mechanisms of accumulation, phenotype, and function. Overarching trends suggest that Tregs can be induced directly by tumor cells and recruited to the tumor microenvironment where they suppress antitumor immunity to facilitate disease progression. Further, we highlight studies showing that Tregs can be modulated by novel therapeutic agents such as immune checkpoint blockade and targeted therapies. Treg disruption by novel therapeutics may beneficially restore immune competence but has been associated with occurrence of adverse events. Strategies to achieve balance between these two outcomes will be paramount in the future to improve therapeutic efficacy and safety.

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Section: Expression Of Inhibitory Receptors and Immune Checkpoint Blo...mentioning

confidence: 71%

Section: Expression Of Inhibitory Receptors and Immune Checkpoint Blo...mentioning

confidence: 99%

Regulatory T cells (Tregs) in lymphoid malignancies and the impact of novel therapies

et al. 2022

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“…Taken together, the irMPs may capture interactions between exhausted lymphocytes and other cell types at baseline, which have been associated with poor response in anti-PD1 immunotherapy. 80 , 81 , 82 …”

Section: Resultsmentioning

confidence: 99%

Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles

He,

Gubin,

Rafei

et al. 2024

iScience

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“…We observed that the top 10 selected irMPs all have high activities in doublets that are enriched in non-responders at baseline (Figure S13). Taken together, the irMPs may capture interactions between exhausted lymphocytes and other cell types at baseline, which have been associated with poor response in anti-PD1 immunotherapy [80][81][82] .…”

Section: Irmps Better Distinguish Immune Checkpoint Blockade (Icb) Re...mentioning

confidence: 99%

Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles

He,

Gubin,

Rafei

et al. 2024

Preprint

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Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy, have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA-seq datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated that these gene sets can be applied to refine pan-cancer immune subtypes, improve ICB response prediction and functionally annotate spatial transcriptomic data. These functional gene sets, informing diverse immune states, will advance our understanding of immunology and cancer research.

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Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma

Cited by 8 publications

References 46 publications

Regulatory T cells (Tregs) in lymphoid malignancies and the impact of novel therapies

Regulatory T cells (Tregs) in lymphoid malignancies and the impact of novel therapies

Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles

Elucidating immune-related gene transcriptional programs via factorization of large-scale RNA-profiles

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