Ziwen Zhu

The paradoxical role of IL-10 in immunity and cancer

Interleukin-10 (IL-10) produced by a wide-variety of cells is a highly pleiotropic cytokine. It has been implicated in the pathogenesis and/or development of autoimmune diseases and cancer, although it displays differential effects that seem to be contradictory sometimes. The ultimate role of this cytokine in disease, however, cannot be fully determined until the immunological contexts that regulate its function are further elucidated. In this review, we will discuss a wide variety of evidence of IL-10 in immunity and cancer in an effort to illuminate the remaining mysteries in the function of this cytokine that, when fully understood, may prove to be a powerful tool in the battle against cancer.

The role of IL-11 in immunity and cancer

Interleukin-11 (IL-11) is a member of the glycoprotein-130 (GP-130) cytokines that utilizes the GP-130 signaling pathway shared by other cytokines of the same family. Traditionally regarded as an anti-inflammatory cytokine, IL-11 also demonstrates its role as a proinflammatory cytokine, suggesting its complex role in immune response. In recent years, IL-11 has an emerging role in various inflammation-associated cancers. In this review, we aim to discuss IL-11 signaling pathway, to explore the role of IL-11 in immunity and various cancers, and to provide a therapeutic perspective of strategies utilized to interfere IL-11 signaling in cancer cells.

IL‐9 inhibits HTB‐72 melanoma cell growth through upregulation of p21 and TRAIL

IL‐9 is a pleiotropic cytokine produced mainly by Th9 cells. IL‐9 may have an anti‐proliferative role in murine melanoma, however, its effect on human melanoma is unknown.

The role of IL-37 in cancer.

Interleukin 37 (IL-37) is a new member of the IL-1 family which all have a similar β-barrel structure. Since its discovery, IL-37 has been studied extensively in immunological field. It has been established that IL-37 possesses anti-inflammatory characteristics both in innate immune response as well as in acquired immune responses by downregulating pro-inflammatory molecules. This review will discuss the role of IL-37 in immunological processes and neoplastic pathogenesis.

Trichomonas vaginalis: a possible foe to prostate cancer.

Prostate cancer (PCA) is the most common malignancy in men in USA, and the role of Trichomonas vaginalis (T. vag) in the development of PCA is still controversial. Clonogenic assay, PCNA staining, TUNEL staining and caspase-3 activity assay were used to investigate the in vitro role of T. vag in human prostate cancer. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. Culture supernatant of T. vag inhibits growth of PC-3 prostate cancer cells, and this correlated with upregulation of p21. Culture supernatant of T. vag induced apoptosis of PC-3 cells, and this correlated with downregulation of Bcl-2. The growth inhibition effect of culture supernatant of T. vag is also demonstrated in another prostate cancer cell line DU145, suggesting that its effect is not specific to one prostate cancer cell line. Culture supernatant of T. vag inhibits growth of prostate cancer by inhibition of proliferation and promotion of apoptosis. Such a study might be helpful to address the association between PCA and infection of T. vag.

IL-32α has differential effects on proliferation and apoptosis of human melanoma cell lines.

Interleukin‐32 (IL‐32) is a recently recognized intracellular, proinflammatory cytokine which may play a role in cancer metastasis and patient survival. The role of IL‐32 in cancer, especially its direct effect on cancer cells, is not well understood.

IL-33 acts as a foe to MIA PaCa-2 pancreatic cancer

IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33. TUNEL+ cells and the relative caspase-3 activity in cancer cells were increased in the presence of IL-33. We further found that its anti-proliferative effect on cancer cells correlated with downregulation of pro-proliferative molecules cdk2 and cdk4 and upregulation of anti-proliferative molecules p15, p21 and p53. Its pro-apoptotic effect correlated with downregulation of anti-apoptotic molecule FLIP and upregulation of pro-apoptotic molecule TRAIL. These results suggest that IL-33 presents significant anti-tumor effects by inhibition of proliferation and induction of apoptosis of MIA PaCa-2 pancreatic cancer cells. Thus, strength of IL-33/ST2 signal pathway might be a promising way to treat pancreatic cancer.

The role of IL-29 in immunity and cancer

Abstract Interleukin-29 (IL-29) is a new member of the recently discovered interferon λ (IFNλ) family. It is produced predominantly by maturing dendritic cells and macrophages. It has been implicated in numerous immunological responses and has shown antiviral activity similar to the Type I interferons, although its target cell population is more limited than the Type I interferons. In recent years, the role of IL-29 in the pathogenesis of various cancers has also been extensively studied. In this review, we will discuss the recent advances of IL-29 in immunological processes and the pathogenesis of various cancer.

Blueberry as a Potential Radiosensitizer for Treating Cervical Cancer

Cervical cancer (CC) is a leading cause of death in women worldwide. Radiation therapy (RT) for CC is an effective alternative, but its toxicity remains challenging. Blueberry is amongst the most commonly consumed berries in the United States. We previously showed that resveratrol, a compound in red grapes, can be used as a radiosensitizer for prostate cancer. In this study, we found that the percentage of colonies, PCNA expression level and the OD value of cells from the CC cell line SiHa were all decreased in RT/Blueberry Extract (BE) group when compared to those in the RT alone group. Furthermore, TUNEL+ cells and the relative caspase-3 activity in the CC cells were increased in the RT/BE group compared to those in the RT alone group. The anti-proliferative effect of RT/BE on cancer cells correlated with downregulation of pro-proliferative molecules cyclin D and cyclin E. The pro-apoptotic effect of RT/BE correlated with upregulation of the pro-apoptotic molecule TRAIL. Thus, BE sensitizes SiHa cells to RT by inhibition of proliferation and promotion of apoptosis, suggesting that blueberry might be used as a potential radiosensitizer to treat CC.

Unveil the mysterious mask of cytokine-based immunotherapy for melanoma

Melanoma is the leading cause of death among all skin cancers and its incidence continues to rise rapidly worldwide in the past decades. The available treatment options for melanoma remain limited despite extensive clinical research. Melanoma is an immunogenic tumor and great advances in immunology in recent decades allow for the development of immunotherapeutic agents against melanoma. In recent years, immunotherapy utilizing cytokines has been particularly successful in certain cancers and holds promise for patients with advanced melanoma. In this review, an overview of the current status and emerging perspectives on cytokine immunotherapy for melanoma are discussed in details. Such a study will be helpful to unveil the mysterious mask of cytokine-based immunotherapy for melanoma.