CD137 enhances cytotoxicity of CD3+CD56+ cells and their capacities to induce CD4+ Th1 responses

Zhu, Biqing; Ju, Shaoqing; Shu, Yongqian

doi:10.1016/j.biopha.2008.10.003

Cited by 17 publications

(21 citation statements)

References 24 publications

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“…Stimulation of these cells with agonistic anti-4-1BB mAbs significantly inhibited their AICD, enhanced their cell division, and increased their cytolytic activity against melanoma cells (28). Similarly, stimulation of human CD3þCD56þ NK cells with anti-4-1BB increased their cytolytic activity, as shown by their ability to lyse A549 tumor cells (29). Cytokine-induced killer cells, generated in vitro by stimulation with anti-CD3/IL-2/IFN-g, are potent anticancer agents (30,31).…”

Section: Anti-4-1bb Mabs As Anticancer Agentsmentioning

confidence: 92%

“…Cytokine-induced killer cells, generated in vitro by stimulation with anti-CD3/IL-2/IFN-g, are potent anticancer agents (30,31). When a group of SCID mice were engrafted with A549 tumor cells and received in addition anti-4-1BB and cytokine-induced killer cells, their mortality rate was reduced (29). Further analysis revealed increased expression of IFN-g, IL-2, and TNF-a, and decreased expression of TGF-b, IL-4, and IL-10 in CD3þCD56þ cells taken from the treated mice (29).…”

Section: Anti-4-1bb Mabs As Anticancer Agentsmentioning

confidence: 99%

“…When a group of SCID mice were engrafted with A549 tumor cells and received in addition anti-4-1BB and cytokine-induced killer cells, their mortality rate was reduced (29). Further analysis revealed increased expression of IFN-g, IL-2, and TNF-a, and decreased expression of TGF-b, IL-4, and IL-10 in CD3þCD56þ cells taken from the treated mice (29). Taken together, these findings underline the important role of 4-1BB signaling in tumor development, and the therapeutic potential of anti-4-1BB mAbs in cancer therapy.…”

Section: Anti-4-1bb Mabs As Anticancer Agentsmentioning

confidence: 99%

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Immunotherapy of Cancer with 4-1BB

Vinay

Kwon²

2012

Molecular Cancer Therapeutics

163

130

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4-1BB (CD137), a member of the TNF receptor superfamily, is an activation-induced T-cell costimulatory molecule. Signaling via 4-1BB upregulates survival genes, enhances cell division, induces cytokine production, and prevents activation-induced cell death in T cells. The importance of the 4-1BB pathway has been underscored in a number of diseases, including cancer. Growing evidence indicates that anti-4-1BB monoclonal antibodies possess strong antitumor properties, which in turn are the result of their powerful CD8þ T-cell activating, IFN-g producing, and cytolytic marker-inducing capabilities. In addition, combination therapy of anti-4-1BB with other anticancer agents, such as radiation, has robust tumor-regressing abilities against nonimmunogenic or poorly immunogenic tumors. Furthermore, the adoptive transfer of ex vivo anti-4-1BB-activated CD8þ T cells from previously tumor-treated animals efficiently inhibits progression of tumors in recipient mice that have been inoculated with fresh tumors. In addition, targeting of tumors with variants of 4-1BBL directed against 4-1BB also have potent antitumor effects. Currently, a humanized anti-4-1BB is in clinical trials in patients with solid tumors, including melanoma, renal carcinoma, and ovarian cancer, and so far seems to have a favorable toxicity profile. In this review, we discuss the basis of the therapeutic potential of targeting the 4-1BB-4-1BBL pathway in cancer treatment.

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Section: Anti-4-1bb Mabs As Anticancer Agentsmentioning

confidence: 92%

Section: Anti-4-1bb Mabs As Anticancer Agentsmentioning

confidence: 99%

Section: Anti-4-1bb Mabs As Anticancer Agentsmentioning

confidence: 99%

See 1 more Smart Citation

Immunotherapy of Cancer with 4-1BB

Vinay

Kwon²

2012

Molecular Cancer Therapeutics

163

130

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“…These clinical observations suggest that new treatment modalities to enhance host immunity (i.e., NK cells) might improve survival in cancer patients. One of those new treatments that it is currently undergoing clinical trials is anti CD 137 monoclonal antibody [53,54]. CD 137 is a surface glycoprotein that belongs to the tumor-necrosis factor receptor superfamily (TNFRSF) and is expressed by activated natural killer cells, T cells, and dendritic cells [53,54].…”

Section: Cut-off Values Of Absolute Lymphocyte Count and Absolute Lymmentioning

confidence: 99%

“…One of those new treatments that it is currently undergoing clinical trials is anti CD 137 monoclonal antibody [53,54]. CD 137 is a surface glycoprotein that belongs to the tumor-necrosis factor receptor superfamily (TNFRSF) and is expressed by activated natural killer cells, T cells, and dendritic cells [53,54]. In vivo studies have shown that anti CD137 enhances cytotoxicity of NK cells and induces a CD4+Th1 response [53].…”

Section: Cut-off Values Of Absolute Lymphocyte Count and Absolute Lymmentioning

confidence: 99%

Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

Porrata¹,

Markovic²

2010

SRX Medicine

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The role of host immunity in cancer clinical outcomes has been wellestablished in animal models. In humans, the impact of the immune system as a therapeutic maneuver to treat malignancies has been proven by the development of graft-versus-tumor effect observed in the allogeneic stem cell transplantation. However, with few notable exceptions, no definitive conclusions have been reached as to the role of host immunity in humans and its impact on cancer outcomes. This article reviews the clinical evidence of how human immunity can affect cancer clinical outcomes using the absolute lymphocyte count as a surrogate maker of host immune competence.

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Prognostic Significance of the Microenvironment in Human Papillomavirus Oropharyngeal Carcinoma: A Systematic Review

Baudouin,

Hans,

Lisan

et al. 2023

The Laryngoscope

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ObjectiveThe immune microenvironment of HPV‐associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) (HPV+OPSCCs) differs from that of HPV‐independent oropharyngeal cancers (HPV‐independent OPSCCs). The literature on the subject is very abundant, demanding an organized synthesis of this wealth of information to evaluate the hypothesis associating the favorable prognosis of HPV+OPSCC patients with a different immune microenvironment. A systematic review of the literature was conducted regarding the microenvironment of HPV+OPSCCs.Data SourceMEDLINE/PubMed, Embase, and Cochrane Library databases.Review MethodsA literature search was performed following PRISMA guidelines (Moher D. PLoS Med. 2009). The PEO (Population, Exposure, and Outcome) framework is detailed as follows: P: patients with oropharyngeal squamous cell carcinomas, E: human papillomavirus (HPV), and O: histological and immunological composition of the tumoral microenvironment (TME). No meta‐analysis was performed.ResultsFrom 1,202 studies that were screened, 58 studies were included (n = 6,474 patients; n = 3,581 (55%) HPV+OPSCCs and n = 2,861(45%) HPV‐independent OPSCCs). The presence of tumor‐infiltrating lymphocytes (TIL), CD3+ in 1,733 patients, CD4+ in 520 patients, and CD8+ (cytotoxic T lymphocytes (CTL)) in 3,104 patients, and high levels of PD‐L1 expression in 1,222 patients is strongly correlated with an improved clinical outcome in HPV+OPSCCs.ConclusionThis systematic review provides the most comprehensive information on the immune microenvironment of HPV+OPSCCs to date. Tumor‐infiltrating lymphocytes and PD‐L1 expression are associated with a favorable prognosis. B, CD8+ and resident memory cells densities are higher in HPV+OPSCCs. The importance of myeloid lineages is still a matter of debate and research.Level of EvidenceN/A Laryngoscope, 2023

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CD137 enhances cytotoxicity of CD3+CD56+ cells and their capacities to induce CD4+ Th1 responses

Cited by 17 publications

References 24 publications

Immunotherapy of Cancer with 4-1BB

Immunotherapy of Cancer with 4-1BB

Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

Prognostic Significance of the Microenvironment in Human Papillomavirus Oropharyngeal Carcinoma: A Systematic Review

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