| Summary: | 碩士 === 國立臺灣大學 === 公共衛生碩士學位學程 === 107 === Cancer have been a leading cause of death lasting over 35 years in Taiwan, and hepatocellular carcinoma (HCC) ranks second among top ten cancer mortality rate. Furthermore, World Health Organization announced that HCC causing 788,000 deaths worldwide in 2015 which is in the second place in all types of cancer. According to the investigation of Health Promotion Administration, Ministry of Health and Welfare, HBV-related and HCV-related accounts respectively for 70% and 20% of HCC. Undoubtedly, HCC is an urgent problem in public health.
Tumor infiltrating leukocytes (TILs) are immune cells which surrounding around tumor and which are capable of distinguishing and targeting transformed cells, and eliminate tumor before becoming clinically apparent. Immunotherapy is the new trend for anti-tumor strategy which modulates human body immune response. However, tumor-drive immunosuppression was found in microenvironment which is the main impediment of immunotherapy. There were many research have shown that TILs have effect on prognosis of HCC patients. For example, regulatory T cells (Tregs) generate immunosuppressive response and create the microenvironment tolerance. It may a breakthrough in anti-cancer therapy by realizing the role of TILs in tumor immunity. In the past, the majority of published research focused on different TILs in HCC, relatively, very few studies had comprehensively addressed HCC separated into HBV-related or HCV-related. This research will explore the association between TILs and prognosis in B-HCC, C-HCC and HCC and compare the difference of TILs influence on HCC with different virus status.
There are 828 patients among six datasets in this study, and divided into three groups, B-HCC (HBV-related HCC; n=313), C-HCC (HCV-related HCC; n=135) and HCC (n=828). This study proposes developed methods, ESTIMATE and CIBERSORT, to assess the immune score which implicated the quantity of leukocytes and the relative proportion among 22 immune cell in tumor/non-tumor tissue through gene expression microarray profile. Thus, we can understand the overview of TILs in tissue and the prognostic difference in HCC with different virus status.
We observed that the density of infiltrating leukocytes in non-tumor is more than in tumor, and the fraction of TILs between B-HCC, C-HCC, HCC are quite different, may related to the virus status. The percentage of TILs in tumor is significantly different from in non-tumor which was found 12, 4 and 12 kinds of immune cells in B-HCC, C-HCC and HCC, respectively. As can be seen that M0 macrophage and CD8 T cell have the same pattern in these three groups. On the other hand, there are different immune cells affecting survival within three groups, whereas, activated dendritic cell and M0 macrophage in B-HCC and HCC groups have the same infiltrating scenario and both have negative effect on survival simultaneously.
We demonstrate the immune cells which participate in the process of carcinogenesis under the influence of tumor microenvironment and directly affect survival in three groups may represents potential targets for future immunotherapy, meanwhile, it suggests that we make different considerations and adjustments regarding different types of virus status to improve therapeutic efficacy.
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