Evaluation of the cytotoxic response mediated by perforin and granzyme B in patients with non-Hodgkin lymphoma

Souza, Bruna Maria Bereta de; Vito, Fernanda Bernadelli De; Calado, Marianna Licati; Silva, Marcos; Oliveira, Leonardo Rodrigues de; Rodrigues-Júnior, Virmondes; Moraes‐Souza, Helio

doi:10.1080/10428194.2017.1341978

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…Similarly, in patients with advanced stage lung cancer, a greater number of CTLs expressing perforin was associated with increased survival (Xu, et al, 2015). Moreover, a previous study by our group also showed that expression of these genes correlated positively with survival time in patients with non-Hodgkin's lymphoma (Souza, et al, 2018).…”

Section: Discussionsupporting

confidence: 56%

Perforin and granzyme B gene expression is associated with a short survival time in patients with multiple myeloma

Souza

Vito

Calado

et al. 2022

RSD

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Objectives: Perforin and granzyme B are essential proteins for protective immune responses mediated by Cytotoxic T Lymphocytes (CTLs) and Natural Killer cells (NK) against cancers, especially those of hematological origin. Our study investigated polymorphisms in the perforin gene (PRF1) and quantified the levels of the perforin and granzyme B proteins in patients with multiple myeloma (MM). Methods: The PRF1 coding region was evaluated in 58 patients with MM and 78 healthy individuals using direct sequencing. Quantitative real-time PCR was performed to quantify gene expression, and flow cytometry was used to determine the intracellular protein levels. Results: We did not observe differences in the allele frequencies of polymorphisms in the PRF1 gene as well as in perforin and granzyme B protein expression between patients with MM and healthy individuals. However, reduced expression of perforin or granzyme B genes was associated with a shorter survival time. In addition, patients with MM had significantly more CTLs expressing perforin and granzyme B, and had an increased number of NK cells. Conclusion: Our study suggests that the gene expression profile of perforin and granzyme B is a potential prognostic marker for MM.

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Section: Discussionsupporting

confidence: 56%

Perforin and granzyme B gene expression is associated with a short survival time in patients with multiple myeloma

Souza

Vito

Calado

et al. 2022

RSD

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“…[61] Lenalidomide is known to enhance the proliferation of NK cells in hematological cancers. [62] In our studies, granzyme B increased upon treatment with lenalidomide in activated immune cell spheroids. Additionally, the release of granzyme B in the activated NHL spheroids was relatively higher at 24 hours compared to 72 hours.…”

Section: Discussionsupporting

confidence: 54%

Microfluidic assembly of hydrogel-based immunogenic tumor spheroids for evaluation of anticancer therapies and biomarker release

Sabhachandani

Sarkar

McKenney

et al. 2019

Journal of Controlled Release

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Diffuse large B cell lymphoma (DLBCL), the most common subtype of Non-Hodgkin lymphoma, exhibits pathologic heterogeneity and a dynamic immunogenic tumor microenvironment (TME). However, the lack of preclinical in vitro models of DLBCL TME hinders optimal therapeutic screening. This study describes the development of an integrated droplet microfluidics-based platform for high-throughput generation of immunogenic DLBCL spheroids. The spheroids consist of three cell types (cancer, fibroblast and lymphocytes) in a novel hydrogel combination of alginate and puramatrix, which promoted cell adhesion and aggregation. This system facilitates dynamic analysis of cellular interaction, proliferation and therapeutic efficacy via spatiotemporal monitoring and secretome profiling. The immunomodulatory drug lenalidomide had direct antiproliferative effect on activated B-cell like DLBCL spheroids and reduced several cytokines and other markers (e.g., CCL2, CCL3, CCL4, CD137 and ANG-1 levels) compared with untreated spheroids. Collectively, this novel spheroid platform will enable high-throughput anti-cancer therapeutic screening in a semi-automated manner.

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“…In the context of NHLs, NK cells have impaired degranulation capacity. According to previous studies, NK cells exhibit defects in the production and exocytosis of cytotoxic granules containing perforin and granzyme [ 93 , 94 ]. In a protein quantification study involving 12 patients with NHL, it was discovered that while the gene expression levels of perforin and granzyme B were higher in NHL patients compared to the control group, the intracellular levels of perforin in NK cells were lower in NHL patients [ 93 ].…”

Section: Nk Cell Defects In Nhlmentioning

confidence: 99%

“…According to previous studies, NK cells exhibit defects in the production and exocytosis of cytotoxic granules containing perforin and granzyme [ 93 , 94 ]. In a protein quantification study involving 12 patients with NHL, it was discovered that while the gene expression levels of perforin and granzyme B were higher in NHL patients compared to the control group, the intracellular levels of perforin in NK cells were lower in NHL patients [ 93 ]. Furthermore, a separate study conducted by Baychelier et al found that patients who developed NHL after undergoing lung transplantation exhibited an accumulation of NK cells with low expression of perforin and impaired degranulation against NHL target cells [ 94 ].…”

Section: Nk Cell Defects In Nhlmentioning

confidence: 99%

Harnessing natural killer cells for refractory/relapsed non-Hodgkin lymphoma: biological roles, clinical trials, and future prospective

Bakhtiyaridovvombaygi,

Yazdanparast,

Kheyrandish

et al. 2024

Biomark Res

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Non-Hodgkin lymphomas (NHLs) are heterogeneous and are among the most common hematological malignancies worldwide. Despite the advances in the treatment of patients with NHLs, relapse or resistance to treatment is anticipated in several patients. Therefore, novel therapeutic approaches are needed. Recently, natural killer (NK) cell-based immunotherapy alone or in combination with monoclonal antibodies, chimeric antigen receptors, or bispecific killer engagers have been applied in many investigations for NHL treatment. The functional defects of NK cells and the ability of cancerous cells to escape NK cell-mediated cytotoxicity within the tumor microenvironment of NHLs, as well as the beneficial results from previous studies in the context of NK cell-based immunotherapy in NHLs, direct our attention to this therapeutic strategy. This review aims to summarize clinical studies focusing on the applications of NK cells in the immunotherapy of patients with NHL.

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Evaluation of the cytotoxic response mediated by perforin and granzyme B in patients with non-Hodgkin lymphoma

Cited by 5 publications

References 26 publications

Perforin and granzyme B gene expression is associated with a short survival time in patients with multiple myeloma

Perforin and granzyme B gene expression is associated with a short survival time in patients with multiple myeloma

Microfluidic assembly of hydrogel-based immunogenic tumor spheroids for evaluation of anticancer therapies and biomarker release

Harnessing natural killer cells for refractory/relapsed non-Hodgkin lymphoma: biological roles, clinical trials, and future prospective

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