1. 논문관련 분야의 소개, 동향, 전망을 설명, 연구과정에서 생긴 에피소드 Immune checkpoint blockade therapy has been revolutionized the field of immuno-oncology and there are world wide efforts to understand the response and resistance mechanisms of action as well as to develop ideal combination strategies to improve patient outcome. There are many potential biomarkers to predict response, however, none of them are available in clinical practice yet. Our group has been studying response and resistance mechanism of PD-1 blockade by utilizing next generation sequencing (whole exome, transcriptome, etc) and various other techniques to characterize tumor microenvironment. Luckily, we were able to generate cell lines from patient's tumor biopsy who had 2 years of durable response, then suffered from rapid relapse. When we assessed the whole exome sequencing of this patient's pre-treatment and post-relapse setting, JAK2 homozygous mutation stood out that accompanied loss of heterozygousity. In vitro studies of these cell lines proved that the patient's tumor lost interferon gamma signaling upon relapse that resulted in loss of interferon mediated immune gene signature demonstrated by nanoString technology. We also found JAK1 homozygous mutation from one of patient who relapsed after long durable response. (no cell line available for this patient). This observation was quite perplexing (Zaretsky et al, NEJM 2016) and we immediately sought potential association between loss of interferon signaling and resistance among patients who did not respond to PD-1 blockade (primary or innate resistance). As my paper described, we identified one patient from melanoma cohort and one patient from mismatch repair deficient colorectal cancer cohort who harbored JAK1 homozygous loss of function mutations. This led us to expand our study on 48 human melanoma cell lines to identify such tumors with loss of adaptive PD-L1 expression due to loss of interferon signaling. 3 out 48 cell lines were not able to up-regulate PD-L1, 2 of them harbored JAK1 or JAK2 loss of function mutation. We proved the cause and effect by JAK1 knock-in or knock-out experiments and analyzed public data base to assess the frequency of JAK1 or JAK2 loss of function mutations as well as clinical outcome of the patients across the histologies (TCGA). Our data showed that though the frequency is low in general, patients who harbor loss of function mutations have poor prognosis in some of major cancer types. This indicates that when cancer cell loses its interferon signaling, it may acquire growth advantage by losing interferon mediated growth arrest or apoptosis. It is becoming clear that tumor interferon signaling plays a significant role in mediating anti-tumor activity to PD-1 blockade or other type of immunotherapy. As we understand more on the tumor interferon signaling related to response and resistance to cancer immunotherapy, I anticipate that we will be able to generate strategies to treat those tumors by combining immunotherapy and potential novel targeted therapy or existing cytotoxic or biologic therapy. 2. 연구를 진행했던 소속기관 또는 연구소에 대해 소개 부탁 드립니다. UCLA is globally well known institution given the significant contributions to medicine, especially cancer medicine by bringing new therapeutics to patients with advanced cancer, such as trastuzumab, gleevec, GM-CSF, enzalutamide and palbociclib, etc. UCLA is also dedicated to train next generation physician scientist to lead the field. The prime example is a STAR (Specialty Training and Advanced Research: total 5 years) program which is combined clinical fellowship and interdepartmental PhD program. I participated this program since 2nd year of medical oncology fellowship training and now expecting to complete the PhD part of training in middle of next year. 3. 연구활동 하시면서 평소 느끼신 점 또는 자부심, 보람 Basic/translational or clinical research require substantial amount of time, efforts and money to produce measurable products. And we are not always to harvest the fruits of our hard work. In addition, the funding environment is not friendly these days in United States. However, I believe that the driving force for us to continue our work is passion to advance science in order to benefit our family, society, community, nation and beyond. I am happy that I was able to produce meaningful product and this will certainly boost my energy to move forward. 4. 이 분야로 진학하려는 후배들 또는 유학준비생들에게 도움이 되는 말씀을 해 주신다면? Cancer biology/immuno-oncology is rapidly evolving and is currently leading the biomedical research. If you are interested in biology and medicine, this is a very hot area and you will have a lot of opportunity to participate. Main thing is to find the right mentor and dive yourself into it so that you are well equipped to interact with experts in this field. 5. 연구활동과 관련된 앞으로의 계획이 있으시다면? I will be joining UCLA as a faculty coming July, 2017 and planning to continue my research work by building upon what I have done over the past 3 and half years. My ambitious goal is to merge tumor immunology with cancer epigenetics and cancer metabolomics. 6. 다른 하시고 싶은 이야기들.... I would like to thank to my mentor for this work and also thank to BRIC staff members for introducing my work.