慶應医学会例会

下記のとおり例会を開催いたしますので、ふるってご来聴くださいますようお願い申し上げます。

日 時 2019 年 9 月 30 日 (月) 18 : 00
場 所 総合医科学研究棟1階ラウンジ
演 題

Dissecting resistance to PD-1 blockade, one cell at a time

  Drew Mark Pardoll M.D., Ph. D.
Department of Pathology, Johns Hopkins University School of Medicine
  PD-1 pathway blockade has been approved for 16 different cancer types and is being tested in an additional 15. Despite its dramatic activity, the majority of patients do not respond to anti-PD-1 antibodies. We have shown that neoadjuvant anti-PD-1 given to lung cancer patients prior to resection of their primary tumor results in a nearly 50% major pathologic response rate (<10% of tumor bed consisting of viable tumor cells). This clinical format allowed us to obtain large numbers of TIL after anti-PD-1 therapy so that we could perform single cell transcriptomics and TCR repertoire analysis. As part of this analysis we could determine which genes and genetic programs were associated with successful anti-tumor response vs non-response. We found that T cells from non-responding tumors exhibited a broad stress response signature, while T cells from MPR tumors did not. While T cells from both responding and non-responding tumors expressed high levels of PD-1, PD-1+ T cells from non-responding tumors had higher levels of the canonical exhaustion factor TOX and other exhaustion-associated genes, including CD39, Tim3 and other checkpoints. T cells from non-responders demonstrated Treg from non-responding tumors were more numerous and expressed specific Treg inhibitory molecules. Taken together, T cells ronr-responding tumor encounter a high stress microenvironment and express high levels of transcriptional and membrane inhibitory molecules, some of which are therapeutically targetable.
演 題

PD-1 blockade a common denominator for cancer therapy

  Suzanne Louise Topalian M.D.
Department of Surgery and Oncology, Johns Hopkins University School of Medicine
  The PD-1 pathway, including the immune cell receptor Programmed Cell Death 1 (PD-1) and its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), mediates immunosuppression in the tumor microenvironment. Drugs that "release the brakes" on anti-tumor immunity by blocking PD-1 or PD-L1 have shown substantial and durable activity in multiple cancers, validating them as a "common denominator" for cancer therapy. Since September 2014, the US FDA has approved 6 different PD-1/PD-L1 antibodies to treat advanced cancers, including 15 tumor types and the broad genetically-defined MSI-high category. These drugs are now being applied in earlier stages of cancer, in the adjuvant and neoadjuvant settings. Tumor PD-L1 protein expression correlates with enhanced responsiveness of some cancers to anti-PD-1, while tumor mutational burden, reflecting neoantigen load, associates with likelihood of response in additional patients. The continued interrogation of potential biomarkers is expected to further refine the risk:benefit profile for PD-1/PD-L1 antagonists, increase our understanding of the mechanistic underpinnings of this pathway, and guide the development of more effective combination therapies.
担 当

先端研(細胞) 教室
責任者:河上 裕 特任教授
担当者:谷口智憲 先生(内線 62708)

  以上
日 時 2019 年 9 月 24 日 (火) 17 : 00
場 所 臨床研究棟1階ラウンジ
演 題

Angiogenic factors: clinical implications in the management of preeclampsia

  Sofia Cerdeira MD, PhD
Nuffield Department of Obstetrics and Gynaecology, University of Oxford
  Preeclampsia is a complex disease with significant maternal and fetal morbidity and mortality. Its syndromic nature makes diagnosis and management difficult. Angiogenic factors, in particular soluble fms-like tyrosine kinase 1 (sFlt-1), have emerged as important molecules in the pathogenesis of preeclampsia and are regarded as potential biomarkers and therapeutic targets. We were the first unit in UK to implement sFlt1/PlGF ratio in clinical practice and are helping other units to do so. I will present our latest data and discuss present and future clinical implications on the use of angiogenic factors in the management of preeclampsia.
担 当

産婦人科学(産科学) 教室
責任者:田中 守 教授
担当者:池ノ上 学 先生(内線 62381)

 
  以上
日 時 2019 年 8 月 19 日 (月) 17 : 00
場 所 総合医科学研究棟1階ラウンジ
演 題

Transcriptional programs underlying T cell exhaustion: Nr4a limits CAR T cell function in solid tumors

  Joyce Chen MD/PhD
La Jolla Institute
参考 固形癌のCAR-T療法におけるT細胞疲弊の分子機構の解明の話。
Nature. 2019 Mar;567(7749):530-534.
NR4A transcription factors limit CAR T cell function in solid tumours.
担 当

微生物学・免疫学教室 教室
責任者:吉村 昭彦 教授
担当者:(内線 61220)

 
  以上
日 時 2019 年 7 月 10 日 (水) 17 : 00
場 所 1号館2階カンファレンスルーム2
演 題

Surgical training and research in the Netherlands

  Bas P.L. Wijnhoven MD PhD
Erasmus University Medical Center Rotterdam The Netherlands
  In contrast to many other countries, training of medical specialists is funded by the Department of Health. The curriculum of medical specialist training including general surgery is well structured and lasts 5-6 years. Specialist (trainers) and hospitals involved in surgical training have been accredited by the Dutch Association of Surgeons. Surgical training includes 4 years of general surgery followed by two years of differentiation in one of the sub-specialities. These are gastrointestinal, oncological, vascular, pediatric and trauma surgery. The training program is competency based: there are key procedures and so called EPA (entrusted professional activities) that are defined to monitor the progress of an individual. Unique in the Dutch system is the quality control and governance of surgical training that will be discussed in my lecture.
The number of positions available for surgical trainees is limited and determined by the government each year. Hence, to enter surgical training has always been very competitive and not easy for young doctors. This is one of the reasons why many students start a PhD program after medical school and to gain experience in basic or clinical research. These young and talented students usually work for 3-4 years full time and are well capable of coordinating trials. This is just one of the reasons that many clinical (randomised) studies come from the Netherlands. Besides this strong academic environment, lack of private practice, strong multidisciplinary working parties and the geographical situation in our small country facilitates multicenter studies. Some more crucial factors for success will be discussed in the lecture.
 
担 当

外科学(一般・消化器) 教室
責任者:北川雄光 教授
担当者:真柳修平 先生(内線 62334)

 
  以上
日 時 2019 年 7 月 8 日 (月) 18 : 30
場 所 リサーチパーク1階 ラウンジ
演 題

Rapidly evolving strategies for the treatment of liver cancer

  Dan G Duda D.M.D., Ph.D.
Massachusetts General Hospital Research Institute, Harvard Medical School
担 当

外科学 教室
責任者:北川 雄光 教授
担当者:茂田 浩平 先生(内線 62234)

 
  以上
日 時 2019 年 6 月 25 日 (火) 17 : 30
場 所 総合医科学研究棟2階会議室
演 題

Dementia care and research - What a difference a decade makes?

  Louise Robinson Professor
Newcastle University Institute of Ageing
  Dementia care currently costs the UK 21 bn pounds a year, and that doesn't include the huge informal costs of family careers and community support networks. Developing services to meet the needs of patients with complex health problems must involve service users. Professor Robinson has addressed what resources are needed to provide a better quality of care, and how these can be successfully delivered to patients and their family. As Newcastle University's Professor of Primary Care and Ageing, and as a working GP in a Newcastle practice, she is keen to ensure that the benefits of the University's excellent research into ageing and the diseases of old age are translated into high quality treatment and care for older people. She leads the Primary Care Group of the Dementia and Neurodegenerative Diseases Research Network (DeNDRoN), a national network of researchers which aims to explore the whole spectrum of dementia care from diagnosis and early detection, through to advanced dementia and end of life care. Another Professor Robinson's ambitions would be to help create a center of excellence at Newcastle University for training GPs, hospital staff, community nurses and others in all aspects of dementia care. In this lecture, Prof Robinson will talk about how her translational research had influenced UK practice over the last 10+ years and at same time bring in her career development in both clinical and academic field.  
担 当

総合診療科 教室
責任者:藤島 清太郎 准教授
担当者:新井 康通 先生(内線 62855)

 
  以上
日 時 2019 年 5 月 10 日 (金) 17 : 00
場 所 東校舎1階会議室
演 題

Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation.

  三澤拓馬
University of Texas Southwestern (UTSW) Medical Center
Center for the Genetics of Host Defense
(ノーベル賞受賞のBruce Beutler研究室)研究員
  変異マウスを用いたフォワード・ジェネティクススクリーニングによって、Immunoglobulin E (IgE) の産生に関わる遺伝子の特定を試みた。その結果、Ser/Thr kinase であるProtein kinase D2 (Prkd2)が、IgE 産生機構の負の制御因子であることが明らかとなった。Prkd2 変異 マウスにおけるIgE の異常な産生は、T follicular helper cells (TFH) の過度の分化に起因していた。
未刺激条件下のCD4+ T細胞において、Prkd2 はTFH のマスターレギュレーターであるB-cell lymphoma 6 (Bcl6)をリン酸化する。リン酸化型Bcl6は核へスムーズに移行できないため、TFHの分化が抑制される。一方、アレルゲン感作によってCD4+ T細胞におけるBcl6 の発現量が高まると、Bcl6 は自身の転写抑制活性によってPrkd2 の転写量を低下させる。Prkd2 の発現量が減少すると、CD4+ T 細胞内には非リン参加型のBcl6 が蓄積し、それらは核内へ移行する。Bcl6 は、核内においてTFH の分化を促進するための遺伝子制御を行う。つまり、本研究によってPrkd2-Bcl6 間の相互制御のバランスが、TFH の分化とその後のIgE の産生量を適切に保つ上で極めて重要であることが明らかとなった。
担 当

微生物学・免疫学教室 教室
責任者:吉村 昭彦 教授
担当者:(内線 61220)

 
  以上

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