Lena Batoon

Bio: Lena Batoon is an academic researcher from University of Michigan. The author has contributed to research in topics: Cancer & Tumor microenvironment. The author has co-authored 1 publications. Previous affiliations of Lena Batoon include University of Queensland.

Cross Talk Between Macrophages and Cancer Cells in the Bone Metastatic Environment.

Abstract: The skeleton is a common site for cancer metastases with the bone microenvironment providing the appropriate conditions for cancer cell colonization. Once in bone, cancer cells effectively manipulate their microenvironment to support their growth and survival. Despite previous efforts to improve treatment modalities, skeletal metastases remain with poor prognoses. This warrants an improved understanding of the mechanisms leading to bone metastasis that will aid development of effective treatments. Macrophages in the tumor microenvironment are termed tumor associated macrophages (TAMs) and their crosstalk with cancer cells is critical in regulating tumorigenicity in multiple cancers. In bone metastases, this crosstalk is also being increasingly implicated but the specific signaling pathways remain incompletely understood. Here, we summarize the reported functions, interactions, and signaling of macrophages with cancer cells during the metastatic cascade to bone. Specifically, we review and discuss how these specific interactions impact macrophages and their profiles to promote tumor development. We also discuss the potential of targeting this crosstalk to inhibit disease progression. Finally, we identify the remaining knowledge gaps that will need to be addressed in order to fully consider therapeutic targeting to improve clinical outcomes in cancer patients.

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

Abstract: Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

Abstract: Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

Prognostic Value and Immunological Role of KIFC1 in Hepatocellular Carcinoma

Abstract: As one of the members of the kinesin family, the role and potential mechanism of kinesin family member C1 (KIFC1) in the development of liver hepatocellular carcinoma (LIHC), especially in the immune infiltration, have not been fully elucidated. In this study, multiple databases and immunohistochemistry were employed to analyze the role and molecular mechanism including the immune infiltration of KIFC1 in LIHC. Generally, KIFC1 mRNA expression was overexpressed in LIHC tissues than normal tissues, and its protein was also highly expressed in the LIHC. KIFC1 mRNA expression was correlated with tumor grade and TNM staging, which was negatively correlated with overall survival and disease-free survival. Moreover, univariable and multivariate Cox analysis revealed that upregulated KIFC1 mRNA is an independent prognostic factor for LIHC. The KIFC1 promoter methylation level was negatively associated with KIFC1 mRNA expression and advanced stages and grade in LIHC. The different methylation sites of KIFC1 had a different effect on the prognosis of LIHC. Specifically, the KIFC1 mRNA expression level showed intense correlation with tumor immunity, such as tumor-infiltrating immune cells and immune scores as well as multiple immune-related genes. Moreover, KIFC1 co-expressed with some immune checkpoints and related to the responses to immune checkpoint blockade (ICB) and chemotherapies. Significant GO analysis showed that genes correlated with KIFC1 served as catalytic activity, acting on DNA, tubulin binding, histone binding, ATPase activity, and protein serine/threonine kinase activity. KEGG pathway analysis showed that these genes related to KIFC1 are mainly enriched in signal pathways such as cell cycle, spliceosome, pyrimidine metabolism, and RNA transport. Conclusively, KIFC1 was upregulated and displayed a prognostic value in LIHC. Moreover, KIFC1 may be involved in the LIHC progression partially through immune evasion and serve as a predictor of ICB therapies and chemotherapies.

Caspase-9 driven murine model of selective cell apoptosis and efferocytosis

Abstract: Apoptosis and efficient efferocytosis are integral to growth, development, and homeostasis. The heterogeneity of these mechanisms in different cells across distinct tissues renders it difficult to develop broadly applicable in vivo technologies. Here, we introduced a novel inducible caspase-9 (iCasp9) mouse model which allowed targeted cell apoptosis and further facilitated investigation of concomitant efferocytosis. We generated iCasp9+/+ mice with conditional expression of chemically inducible caspase-9 protein that is triggered in the presence of Cre recombinase. In vitro, bone marrow cells from iCasp9+/+ mice showed expression of the iCasp9 protein when transduced with Cre-expressing adenovirus. Treatment of these cells with the chemical dimerizer (AP20187/AP) resulted in iCasp9 processing and cleaved caspase-3 upregulation, indicating successful apoptosis induction. The in vivo functionality and versatility of this model was demonstrated by crossing iCasp9+/+ mice with CD19-Cre and Osteocalcin (OCN)-Cre mice to target CD19+ B cells or OCN+ bone-lining osteoblasts. Immunofluorescence and/or immunohistochemical staining in combination with histomorphometric analysis of EGFP, CD19/OCN, and cleaved caspase-3 expression demonstrated that a single dose of AP effectively induced apoptosis in CD19+ B cells or OCN+ osteoblasts. Examination of the known efferocytes in the target tissues showed that CD19+ cell apoptosis was associated with infiltration of dendritic cells into splenic B cell follicles. In the bone, where efferocytosis remains under-explored, the use of iCasp9 provided direct in vivo evidence that macrophages are important mediators of apoptotic osteoblast clearance. Collectively, this study presented the first mouse model of iCasp9 which achieved selective apoptosis, allowing examination of subsequent efferocytosis. Given its unique feature of being controlled by any Cre-expressing mouse lines, the potential applications of this model are extensive and will bring forth more insights into the diversity of mechanisms and cellular effects induced by apoptosis including the physiologically important efferocytic process that follows.