• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.13-24
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• 2024

Cytokines influence the overall cancer immune cycle by triggering tumor antigen expression, antigen presenting, immune cell priming and activation, effector immune cell recruitment and infiltration to cancer, and cancer killing in the tumor microenvironment (TME). Therefore, cytokines have been considered potential anti-cancer immunotherapy, and cytokine-based anti-cancer therapies continue to be an active area of research and development in the field of cancer immunotherapy, with ongoing clinical trials exploring new strategies to improve efficacy and safety. In this review, we examine past and present clinical developments for major anticancer cytokines, including interleukins (IL-2, IL-15, IL-12, IL-21), interferons, TGF-beta, and GM-CSF. We identify the current status and changes in the technology platform being applied to cytokine-based immune anti-cancer therapeutics. Through this, we discuss the opportunities and challenges of cytokine-based immune anti-cancer treatments in the current immunotherapy market and suggest development directions to enhance the clinical use of cytokines as immuno-anticancer drugs in the future.

• BMB Reports
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• v.55 no.1
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• pp.48-56
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• 2022

Small extracellular vesicles (sEVs) secreted by most cells carry bioactive macromolecules including proteins, lipids, and nucleic acids for intercellular communication. Given that some immune cell-derived sEVs exhibit anti-cancer properties, these sEVs have received scientific attention for the development of novel anti-cancer immunotherapeutic agents. In this paper, we reviewed the latest advances concerning the biological roles of immune cell-derived sEVs for cancer therapy. sEVs derived from immune cells including dendritic cells (DCs), T cells, natural-killer (NK) cells, and macrophages are good candidates for sEV-based cancer therapy. Besides their role of cancer vaccines, DC-shed sEVs activated cytotoxic lymphocytes and killed tumor cells. sEVs isolated from NK cells and chimeric antigen receptor (CAR) T cells exhibited cytotoxicity against cancer cells. sEVs derived from CD8⁺ T and CD4⁺ T cells inhibited cancer-associated cells in tumor microenvironment (TME) and activated B cells, respectively. M1-macrophage-derived sEVs induced M2 to M1 repolarization and also created a pro-inflammatory environment. Hence, these sEVs, via mono or combination therapy, could be considered in the treatment of cancer patients in the future. In addition, sEVs derived from cytokine-stimulated immune cells or sEV engineering could improve their anti-tumor potency.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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• pp.29-41
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• 2018

Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immunooncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC.

• Korean Journal of Clinical Pharmacy
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• v.31 no.3
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• pp.237-246
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• 2021

Background: Pembrolizumab, an anti-cancer drug, is known to increase the activity of the immune system, leading to side effects called immune-related adverse events (irAE), including type 1 diabetes. This study analyzed the correlation between blood glucose level and pembrolizumab administration and investigated the covariates that affect those changes in cancer treatment. Methods: The information of 133 adult cancer patients was obtained from the electronic medical record (EMR) to identify the changes in random blood glucose (RBG) levels during the pembrolizumab treatment. Subjects were classified into subgroups according to their baseline RBG level, history of diabetes, and the use of steroids, and linear regression analysis was conducted. In addition, a secondary analysis was performed within the group of subjects having a strong correlation to glycemic change, which was based on the Pearson correlation coefficient being less than -0.7 or greater than +0.7. Univariate and multivariate logistic regressions were conducted to identify the risk factors to glycemic increase. Results: The RBG level tended to descend without significant differences in total patients during the administration period of pembrolizumab. Despite the insignificance, the logistic regression analysis presents that the odds ratios of baseline RBG less than 130 mg/dL, prophylactic steroid use, and higher dose of pembrolizumab per cycle (mg/kg/cycle) were greater than 1. Conclusions: Prophylactic administration of steroids and a higher dose of pembrolizumab per cycle may increase the blood glucose level as irAE in cancer patients with a strong tendency to glycemic change.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.60-64
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• 2002

Background: Chemotherapy with 5-fluorouracil (5-FU) has been one of the mainstay in breast cancer treatment. The effects of high dose 5-FU on cell cycle regulation were studied in breast caner cells. Methods: A breast cancer cell line MCF-7 was used. Protein expressions of G1/S cyclins, $p21^{Waf1/Cip1}$, cdk2, E2F1 and retinoblastoma were tested by western blot analysis. Immunoprecipitation and immune complex kinase assay were done for the assessment of E2F1/RB interacton and the activity of cdk2 respectively. Results: $p21^{Waf1/Cip1}$ expression was barely detectable in control cells. With addition of 5-FU level of $p21^{Waf1/Cip1}$ were induced and cyclin D3 level was decreased as cell growth decreases. In accordance with increased expression of $p21^{Waf1/Cip1}$, cyclin E-associated cdk2 kinase activity was reduced. Retinoblastoma protein (RB) became dephosphorylated and E2F-1 binding activity with RB was increased. Conclusion: In this situation of high concentration of 5-FU breast cancer cells tend to be G1/S cell cycle arrested. Overexpression of $p21^{Waf1/Cip1}$ and dephosphorylation of RB may mediate the effectss of 5-FU by inhibiting E2F-1 activity, which contributes to G1/S cell cycle arrest. These results could be an indicating landmark for further study of high dose chemotherapy with 5-FU.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5513-5518
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• 2013

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

• The Journal of Internal Korean Medicine
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• v.41 no.5
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• pp.911-925
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• 2020

Objectives: The purpose of this study was to report a case of a patient with advanced gastric cancer with peritoneal metastasis treated with chemotherapy and Korean medicine Methods: A patient with advanced gastric cancer with peritoneal metastasis was treated with Xeloda/cisplatin since April 2019. The cycle was repeated every three weeks for a total of 11 times. At the same time, the patient was treated with Korean medicine. The tumor size was measured by computed tomography (CT) and esophagogastroduodenoscopy (EGD). Adverse events were evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Results: After treatment with Xeloda/cisplatin and Korean medicine for nine months, the extent of the proximal portion of the primary tumor and the size and number of multiple nodules around the stomach decreased and the cancer cells with peritoneal metastasis disappeared. The symptoms of discomfort and physical activity were gradually improved. As a result, the patient underwent conversion surgery. Conclusions: This case study suggests that the combination of chemotherapy and Korean medicine may contribute to the reduction in tumor size as well as the improvement in the quality of life.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1691-1699
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• 2016

Ovarian cancer is possibly the sixth most common malignancy worldwide, in Mexico representing the fourth leading cause of gynecological cancer death more than 70% being diagnosed at an advanced stage and the survival being very poor. Ovarian tumors are classified according to histological characteristics, epithelial ovarian cancer as the most common (~80%). We here used high-density microarrays and a systems biology approach to identify tissue-associated deregulated genes. Non-malignant ovarian tumors showed a gene expression profile associated with immune mediated inflammatory responses (28 genes), whereas malignant tumors had a gene expression profile related to cell cycle regulation (1,329 genes) and ovarian cell lines to cell cycling and metabolism (1,664 genes).

• Molecules and Cells
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• v.37 no.4
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• pp.286-294
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• 2014

Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key regulator of various cell cycle events that are critical for proper M-phase progression. The polobox domain (PBD) present in Plk1's C-terminal noncatalytic region has been shown to play a central role in targeting the N-terminal kinase domain of Plk1 to specific subcellular locations. Subsequent studies reveal that PBD binds to a phosphorylated motif generated by one of the two mechanisms - self-priming by Plk1 itself or non-self-priming by a Pro-directed kinase, such as Cdc2. Here, we comparatively review the differences in the biochemical steps of these mechanisms and discuss their physiological significance. Considering the diverse functions of Plk1 during the cell cycle, a better understanding of how the catalytic activity of Plk1 functions in concert with its cisacting PBD and how this coordinated process is intricately regulated to promote Plk1 functions will be important for providing new insights into different mechanisms underlying various Plk1-mediated biological events that occur at the multiple stages of the cell cycle.

• Development and Reproduction
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• v.24 no.1
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• pp.53-62
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• 2020

Natural killer (NK) cells are innate lymphocytes that play an essential role in preventing cancer development by performing immune surveillance to eradicate abnormal cells. Since ex vivo expanded NK cells have cytotoxic activity against various cancers, including breast cancers, their clinical potential as immune-oncogenic therapeutics has been widely investigated. Here, we report that the pyrazole chemical XRP44X, an inhibitor of Ras/ERK activation of ELK3, stimulates NK-92MI cells to enhance cytotoxic activity against breast cancer cells. Under XRP44X stimulation, NK cells did not show notable apoptosis or impaired cell cycle progression. We demonstrated that XRP44X enhanced interferon gamma expression in NK-92MI cells. We also elucidated that potentiation of the cytotoxic activity of NK-92MI cells by XRP44X is induced by activation of the c-JUN N-terminal kinase (JNK) signaling pathway. Our data provide insight into the evaluation of XRP44X as an immune stimulant and that XRP44X is a potential candidate compound for the therapeutic development of NK cells.