The synergism of B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) attenuated acute T-cell mediated rejection and prolonged renal graft survival

Zhang, Hengcheng; Wang, Zijie; Zhang, Jiayi; Zhang, Xiang; Gui, Zeping; Sun, Lingyun; Yang, Haiwei; Tan, Ruoyun; Gu, Min

doi:10.21037/tau-20-728

Cited by 4 publications

(4 citation statements)

References 36 publications

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“…Agonistic antiBTLA antibody combined with CTLA-4 immunoglobulin treatment can prolong the survival of islet allografts, while promoting indefinite graft acceptance (110,111). Moreover, according to the latest research, overexpression of BTLA combined with CTLA-4 in kidney transplant recipients reduced IL-2 production, suppressed T cell proliferation, improved graft function, attenuated acute T cell-mediated rejection, and extended graft survival (112). However, there have been some contradictory reports.…”

Section: Btla and Transplantation Rejectionmentioning

confidence: 99%

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Roles of BTLA in Immunity and Immune Disorders

2021

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B and T lymphocyte attenuator (BTLA) is one of the most important cosignaling molecules. It belongs to the CD28 superfamily and is similar to programmed cell death-1 (PD-1) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) in terms of its structure and function. BTLA can be detected in most lymphocytes and induces immunosuppression by inhibiting B and T cell activation and proliferation. The BTLA ligand, herpesvirus entry mediator (HVEM), does not belong to the classic B7 family. Instead, it is a member of the tumor necrosis factor receptor (TNFR) superfamily. The association of BTLA with HVEM directly bridges the CD28 and TNFR families and mediates broad and powerful immune effects. Recently, a large number of studies have found that BTLA participates in numerous physiopathological processes, such as tumor, inflammatory diseases, autoimmune diseases, infectious diseases, and transplantation rejection. Therefore, the present work aimed to review the existing knowledge about BTLA in immunity and summarize the diverse functions of BTLA in various immune disorders.

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Section: Btla and Transplantation Rejectionmentioning

confidence: 99%

“…All the four molecules form the HVEM/BTLA/CD160/ LIGHT signaling network. For HVEM, binding to BTLA mediates the inhibitory effect, while binding to LIGHT (106,(108)(109)(110)(111)(112).…”

Section: Perspectivesmentioning

confidence: 99%

Roles of BTLA in Immunity and Immune Disorders

2021

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“…Three clinical trials using agonistic anti-BTLA antibodies (LY3361237, Stanford University and Eli Lilly and Company and ANB032 from AnaptysBio) are currently undergoing in patients with systemic lupus erythematosus (NCT05123586), Sjogren's syndrome (NCT05781451), and severe atopic dermatitis (NCT05935085). Moreover, agonistic anti-BTLA antibodies have been proposed as a potential therapy to ameliorate GvHD resulting from allogeneic bone marrow transplantation or to prolong allograft survival in models of renal or cardiac transplantation [120][121][122][123][124][125]. Nevertheless, studies targeting BTLA and HVEM are currently under preclinical development.…”

Section: Concluding Remarks and Future Directionsmentioning

confidence: 99%

Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy

Sordo-Bahamonde,

Lorenzo-Herrero,

Granda-Díaz

et al. 2023

Mol Cancer

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Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success of immune checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, the limited overall responses and lack of reliable predictive biomarkers of patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects the compelling need of unveiling novel targets for immunotherapy that allow to expand the spectrum of ICB-based strategies to achieve optimal therapeutic efficacy and benefit for cancer patients. This review thoroughly dissects current molecular and functional knowledge of BTLA/HVEM axis and the future perspectives to become a target for cancer immunotherapy. BTLA/HVEM dysregulation is commonly found and linked to poor prognosis in solid and hematological malignancies. Moreover, circulating BTLA has been revealed as a blood-based predictive biomarker of immunotherapy response in various cancers. On this basis, BTLA/HVEM axis emerges as a novel promising target for cancer immunotherapy. This prompted rapid development and clinical testing of the anti-BTLA blocking antibody Tifcemalimab/icatolimab as the first BTLA-targeted therapy in various ongoing phase I clinical trials with encouraging results on preliminary efficacy and safety profile as monotherapy and combined with other anti-PD-1/PD-L1 therapies. Nevertheless, it is anticipated that the intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved in immune response regulation, tumor development and tumor microenvironment could limit therapeutic success. Therefore, in-depth functional characterization in different cancer settings is highly recommended for adequate design and implementation of BTLA-targeted therapies to guarantee the best clinical outcomes to benefit cancer patients.

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“…Therefore, the inhibition of these interactions with monoclonal antibodies increases their anti-tumor activity. The most common immune checkpoints include cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), T cell immunoglobulin and mucin-3 (TIM-3), B and T lymphocyte attenuator (BTLA), lymphocyte activation gene 3 (LAG3), adenosine 2A receptor (A2AR) and T cell immunoglobulin and ITIM domain (TIGIT) (85)(86)(87)(88)(89)(90)(91). Secreted molecules by tumor cells impact the expression of immunecheckpoint receptors on immune cells.…”

Section: Impact Of Tumor Secretome In the Anti-tumor Activity Of Immune Cells T Cellsmentioning

confidence: 99%

Tumor Secretome to Adoptive Cellular Immunotherapy: Reduce Me Before I Make You My Partner

Etxebeste-Mitxeltorena

Rincón-Loza

Martín-Antonio

2021

Front. Immunol.

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Adoptive cellular immunotherapy using chimeric antigen receptor (CAR)-modified T cells and Natural Killer (NK) cells are common immune cell sources administered to treat cancer patients. In detail, whereas CAR-T cells induce outstanding responses in a subset of hematological malignancies, responses are much more deficient in solid tumors. Moreover, NK cells have not shown remarkable results up to date. In general, immune cells present high plasticity to change their activity and phenotype depending on the stimuli they receive from molecules secreted in the tumor microenvironment (TME). Consequently, immune cells will also secrete molecules that will shape the activities of other neighboring immune and tumor cells. Specifically, NK cells can polarize to activities as diverse as angiogenic ones instead of their killer activity. In addition, tumor cell phagocytosis by macrophages, which is required to remove dying tumor cells after the attack of NK cells or CAR-T cells, can be avoided in the TME. In addition, chemotherapy or radiotherapy treatments can induce senescence in tumor cells modifying their secretome to a known as “senescence-associated secretory phenotype” (SASP) that will also impact the immune response. Whereas the SASP initially attracts immune cells to eliminate senescent tumor cells, at high numbers of senescent cells, the SASP becomes detrimental, impacting negatively in the immune response. Last, CAR-T cells are an attractive option to overcome these events. Here, we review how molecules secreted in the TME by either tumor cells or even by immune cells impact the anti-tumor activity of surrounding immune cells.

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The synergism of B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) attenuated acute T-cell mediated rejection and prolonged renal graft survival

Cited by 4 publications

References 36 publications

Roles of BTLA in Immunity and Immune Disorders

Roles of BTLA in Immunity and Immune Disorders

Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy

Tumor Secretome to Adoptive Cellular Immunotherapy: Reduce Me Before I Make You My Partner

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