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- 검색키워드
- 저자 : Tae Gun Kang (검색결과 2 건)
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Tae Gun Kang 연세대학교, 일반대학원 2021 국내박사
Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as MIP-1 alpha, facilitates the recruitment of dendritic cells for the presentation of tumor antigens and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for preclinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote antitumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is often exacerbated upon coinfection, but the underlying immunological mechanisms remain unclear. Here, to elucidate these mechanisms, we used a TB and lymphocytic choriomeningitis virus coinfection model. Viral coinfection significantly suppressed Mtb-specific IFN-γ production, with elevated bacterial loads and hyperinflammation in the lungs. Type I IFN signaling blockade rescued the Mtb-specific IFN-γ response and ameliorated lung immunopathology. Single-cell sequencing, tissue immunofluorescence staining, and adoptive transfer experiments revealed that type I IFN produced in response to viral infection inhibited CXCL9/10 production in myeloid cells, resulting in impaired pulmonary migration of Mtb-specific CD4+ T cells from lymph nodes. Thus, virus coinfection-induced type I IFN signaling prior to the pulmonary localization of Mtb-specific Th1 cells exacerbates TB immunopathogenesis by impeding the Mtb-specific Th1 cell influx. Our study highlights another novel negative role of viral coinfection and/or type I IFNs in delaying Mtb-specific Th1 responses in the lung.
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웹 상에서 개인화된 정보 제공을 위한 모니터링 에이전트 구조
This paper deecribes a mechanism and its aspects for monitoring user actions and behaviors on the web operated under the layered architecture that utilizes intelligent agents, and by which personalized information services, for instance one-to-one marketing, is easily facilitated and developed. Due to growing concerns on Elcetronic Commerce, some commercial web sites such as shopping stores and malls that are already quite common on the Internet are expected to become more widespread in the near future, because of not only the convenience in opening up and maintaining a store, but also its commercial potentiality in cyber space. Compared with real commerce environment, it can be relatively easy to offer various intelligent services to users on a web site that can draw users interests. Intelligent agent is one of techniques which enable to automate to whole process for providing personalized services that includes monitoring, logging a user actions and analyzing behaviors based on his or her profiles, and then selecting, organizing customizable contents which are at last delivered to the user's browser or mail box also by intelligent agents. This paper proposes an architecture that consists of three conceptual layers, which are web interface layer, intelligent agent layer, and database layer. Under this architectural basis, this paper focuses on studying an effective monitoring technique which can be regarded as a necessary step for providing personalized services. This paper first starts describing some problematic aspects of the web and then proposing a technique called session-based monitoring with intelligent agent so that a web site can log stateful data on its customers which can then be used to find out his or her preferences and interests. In session-based monitoring, the concept of user session is required to maintain so that a web site can detect and log important actions done by a specific user over the given series of requests from the user. Therefore, various kinds of personalized services can be devised and equipped in a commercial web site through adopting and operation session-based monitoring. The proposed monitoring technique was experimented and prototyped with a monitoring agent and a push agent for validation purpose under Java Web Server, with a few servlets in several web documents using scripts. An agent for monitoring user actions was implemented in the bodies of a few servlets, and push agent for delivering personalized contents was implemented in standalone Java applications. Intelligent agent technology can utilize to help better construct the process in providing personalized services in that those services require intelligence in operating and autonomous procedures. As a result, implementing effective personalized services, however, depends on how well to define various users interests and needs, and how correctly to detect and log the actions when they are done by users. The proposed session-based monitoring technique using intelligent agent technology cna fit these requirements and then be considered as one of solutions.
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