The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1Â10 9 PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8 + T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK celldepleted mice and CD8 -/-mice, and partially blocked in CD4 -/-mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.

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For a long time lung cancer was associated with a fatalistic approach by healthcare professionals. In recent years, advances in imaging, improved diagnostic techniques and more effective treatment modalities are reasons for optimism. Accurate lung cancer staging is vitally important because treatment options and prognosis differ significantly by stage. The staging algorithm should include a contrast computed tomography (CT) of the chest and the upper abdomen including adrenals, positron emission tomography/CT for staging the mediastinum and to rule out extrathoracic metastasis in patients considered for surgical resection, endosonography-guided needle sampling procedure replacing mediastinoscopy for near complete mediastinal staging, and brain imaging as clinically indicated. Applicability of evidence-based guidelines for staging of lung cancer depends on the available expertise and level of resources and is directly impacted by financial issues. Considering the diversity of healthcare infrastructure and economic performance of Asian countries, optimal and costeffective use of staging methods appropriate to the available resources is prudent.The pulmonologist plays a central role in the multidisciplinary approach to lung cancer diagnosis, staging and management. Regional respiratory societies such as the Asian Pacific Society of Respirology should work with national respiratory societies to strive for uniform standards of care. For developing countries, a minimum set of care standards should be formulated.Cost-effective delivery of optimal care for lung cancer patients, including staging within the various healthcare systems, should be encouraged and most importantly,tobacco control implementation should receive an absolute priority status in all countries in Asia.

Fractalkine (CX3CL1) is a unique membrane-bound CX3C chemokine that serves as a potent chemoattractant for lymphocytes. The hypothesis of this study is that dendritic cells (DC) genetically modified ex vivo to overexpress fractalkine would enhance the T cell-mediated cellular immune response with a consequent induction of anti-tumor immunity to suppress tumor growth. To prove this hypothesis, established tumors of different mouse cancer cells (B16-F10 melanoma, H-2 b , and Colon-26 colon adenocarcinoma, H-2 d ) were treated with intratumoral injection of bone marrowderived DC that had been modified in vitro with an RGD fiber-mutant adenovirus vector expressing mouse fractalkine (Ad-FKN). In both tumor models tested, treatment of tumor-bearing mice with Ad-FKN-transduced DC gave rise to a significant suppression of tumor growth along with survival advantages in the treated mice. Immunohistochemical analysis of tumors treated with direct injection of Ad-FKN-transduced DC demonstrated that the treatment prompted CD8 + T cells and CD4 + T cells to accumulate in the tumor milieu, leading to activation of immune-relevant processes. Consistent with the finding, the intratumoral administration of Ad-FKN-transduced DC evoked tumor-specific cytotoxic T lymphocytes, which ensued from in vivo priming of Th1 immune responses in the treated host. In addition, the anti-tumor effect provided by intratumoral injection of Ad-FKN-transduced DC was completely abrogated in CD4 + T cell-deficient mice as well as in CD8 + T cell-deficient mice. These results support the concept that genetic modification of DC with a recombinant fractalkine adenovirus vector may be a useful strategy for cancer immunotherapy protocols.

The first coronavirus disease 2019 (COVID-19) cases reported by the Indonesian Government on 2 March 2020 came from Jakarta (population 11 million), the capital city of the Republic of Indonesia. The government appointed a COVID-19 Task Force under the National Disaster Management Authority to coordinate all aspects of the COVID-19 response. 1 At that time, three hospitals in Jakarta, namely the

Legionnaires' disease is clinically manifested as severe pneumonia caused by Legionella pneumophila. However, the dendritic cell (DC)-centered immunological framework of the host defense against L. pneumophila has not been fully delineated. For this study, we focused on a potent chemoattractant for lymphocytes, fractalkine/ CX3CL1, and observed that the fractalkine expression of DCs was somewhat up-regulated when they encountered L. pneumophila. We therefore hypothesized that fractalkine expressed by Legionella-capturing DCs is involved in the induction of T-cell-mediated immune responses against Legionella, which would be enhanced by a genetic modulation of DCs to overexpress fractalkine. In vivo immunization-challenge experiments demonstrated that DCs modified with a recombinant adenovirus vector to overexpress fractalkine (

Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer.