0621-0622 大會報告

Day 1
院長致詞: 十一月份還會有一個retreat

Emerging Trends and Opportunities for Microbiota Research
高承源副研究員 (免疫醫學中心)

– Microbiota is not just about bacteria, viruses, fungi are also included.
– Analytic tools of microbiota (e.g.assembling the human gut Microbiota in metabolic diseases.

– 16S/26S RNA sequencing)
– Metaproteomics workflow
– Models for human microbiota research
– Organ-on-a-chip RootChip (different levels of oxygen at different layers of matrix)
– Ex vivo models for microbiota research
– Experimental approaches for defining functional roles of mirobes in the human gut (PMID: 24024637)
* lost of function
* gain-of function approaches

– Determining causality in animal models
– From human fecal to mice
* germ-free mouse facility in NLAC: isolator
* Isolator at cage level

* Isocage 正壓型等級小鼠飼養機
– Natural product…
– The progression of microbiota research
Observation –> Correlative –> Causative (germ-free mice) –> Mechanistic (still very rare studies)

Microbiome projects
* US NIH HMP type1, type2 diabetes
* The earth microbiome project is. A systematic attempt to
* France
* China
* Crowdfunding microbiome project
* (UCSD) American gut
* Taiwan gut citizen science project
– Microabiota is the new key to finger many diseases
– Gordon lab.: the father of microbiome
$ Yin-yang of obesity ion the gut microbiota
$ an obesity-associated gut microbiome with increased capacity for energy harvest (Nature)
$ Causality: gut bug transmitted obsity 2013/Science
– A microbial protein that alleviates metabolic syndrome (Scientists at Belgium) A.muciniohilia (Akk bacteria)
– Dusp6 knockout mice
– CTLA4 blockade relies on gut microbiota
– How the Microbiota modulate chemotherapy and
– Gut Microbes can shape response to cancer immunotherapy
– Three papers in Science (end of 2017)
– FMT ——>

### Non-antibiotic drugs have effects on gut Microbiota
Nature article: extensive impact of non-antibiotic drugs on human gut bacteria
ClinicalTrials.gov
## Bugs as drugs ## Drug the bugs
## bacterial metabolites ## new biomarkers

– Personalized therapies & precision medicine
# guys bacteria can stop cancer drugs from working

– The microbiome understood by AI
– Microbiota research is multidisplinarity
– Key players in the microbiome (Gordon Lab, Belgium, China, Germany, Sweden)
– Synthetic and metablome
– Computational
– Metabolism and inflammation

2016/May US White House —> The microbiome Project

The most needed Taiwanese microbiome projects
— baseline studies
— healthy subjects
A potentially unique yet important baseline study project tin Taiwan

Fecal Microbiota Transplantation (FMT) for Clostridium Difficile Infection and Other Diseases 邱政洵教授 (林口長庚醫院兒童感染科)

2007年起各國已陸續投入經費支持大型微生物菌相研究計畫

人體微生物菌相 Microbiota 人體第二基因體Microbiome

Microbiome refers to the collective genomes of these microorgamnisms

Munich of understanding of these bodily inhabitants has been derived fro 16S rRNA and metagenomiucs sequecning

Gut contains 1100 prevalent sleepiest and at least 160 species per individual

Human microbiota estimates 109-01009 trillion microbial cells, and the intestine accounts fo the largest and most diverse populations

FMT

— administration o resolution of fecal matter from a do not into the intestinal retract of a recipient to directly changes the recipient’s microbial composition and confers a health benefit

— the first FMT was developed in 1940

— rCDI (C.difficile infection) recurrent C.difficile infection

Research in CDI” Cell 2017 169, p375

• a toxin mediated infectious disease

• Immunotherapy

• Bezlotoxumab for prevention f recurrent C.diff infection (NEJM 2017)

• FMT for rCDI

— most clinical experience with FMT derived form treating recurrent or refractory Clostridioim difficile infection (rCDI)

Quality of evuduenceL high

Strength of recommendation L strong

Tow I open-label RCTs 94% and 90% vs vancomycin 31% and 26%m respoectiuvelky (NEJM, AP&T)

A larger double-blind RCT..

NEJM 2013 Jan 31 (compare FMT and antibiotics therapy)

• improvement in the microbial diversity,m which persisted over time

• Increase in bacteriophages species and Clostridium clostridium IV and XIVa (Firmicutes), and decrease in Proteobacteria

Sterile Fecal Filtrate for rCDI

• stool collected from 5 donors selected by the patients, and fully characterized according to FMT standards

• In all 5 patient, FFT restored normal stroll habits and eliminated symptoms of CDI for a minimum period of 6 months.

——-

Effect of oral capsule- vs colonoscopy-delivered FMT on rCDI (JAMA 2017)

Stool donor and FMT manufacturing pools of 7 healthy donors

• secondary outcome changes in quality of life

• minor adverse events 5-10% (nausea,

• cost capsules (308 USD) versus colono (708? USD)

IBD and IBS (still in investigation stage)

inflammatory bowel disease and inflammatory bowl syndrome

IBD may need multiple transfusions, and has donor effect

IBS placebo effect is required

FMT in the management of IBD, a systematic review and meta-analysis

FMT induces remission one patients with active UC, a RCT

• 75 adult active UC on stable does poses of IUM randomized org weekly FMTs or water enemas x 6 and evaluated for remission (…

Microbial analysis

• an increase in bactericides and proteobacteria

• insole delivery of high-diversity FMP by colonoscopy for active UC

Metabolic syndrome

• FMT in metabolic syndrome should only be performed in a research setting

Microbiome and fish for metabolic syndrome

• not all the published evidence is consistent with the hypothesis

• Much of the literatures are

Multi drug resistant disteas

3 high priority bacterial

Usding FMT to “decolonization” of MDR

Impact of DMT on complete and partial antibiotic resistant bacteria (ARB) decolonization of

Adverse events after decal microbiota transplantation (minor)

ICI (pre-clinical) immune checkpoint inhibitor

Gut microbiome influences efficacy of PD-1` based immunotherapy atainst eputhelial tumors

Enforcement policies

Therapeutic

15-30% refractory fby conventional antibiotics therapy

FMT: ~100% efficacy in the first 6-month, after 2-years still have > 80% efficacy

Taiwan FMT Expert Consensus
吳俊穎主任 (臺北榮民總醫院轉譯研究科) 微菌叢植入治療

1st Characteristics

First Asian FMT consensus

Local is important (在地化)

2nd characteristics

Multiple stakeholders’ consensus (scholars.)

3rd characteristics

Quality assurance by government regulations (special regulations for FMT)

Clinical Trial FMT (fecal microbiota transplantation)

台灣微菌聯盟

Steering committee 2017,/7/18

Major references

Clin gastroenterol hapatol (US FMT workgroup 2011)

J law and biosciences (ioenbiome 2015)

會議內容

2017/09/30 steering committee

基本資料及問卷

Super-donor criteria

2018/2/24 FMT consensus meeting

醫療法第62條

(5) 植入方式

B 經大腸鏡將微菌叢由結腸植入

More AE in the colonoscopy FMT cohort

Abdominal pain, blood in stool, FMT material leakage

Industrila developed FMT capsiule

Seres Therapeutics: SEWR 109

• cohort 1: SER-109 for 2 days (1.7 x 10^9 spores)

• Cohort 2:

Conclusions

• FMT via capsule is effective as FMT biz endoscopy delivery

• Both frozen and

• must be handled in BSL2

• Fees

• Registration

• other diseases suitable for FMT: IBD, resistant bacteria’s, obesity, neuropsychiatric disorders, metabolic syndrome

Gut-brain Axis: a Fundamental Mechanism Modulating Alzheimer’s Progression
莊志立研究員 (分子與基因醫學研究所)

2012 Cell host and Microbes

Infection-induced intestinal oxidative stress…

Neurologiocal diseases may be affected by intestinal microbiota

Immune hemocyte (invertebrate) = plasmatocytes (verterrate)

Enteric infection facilitates immune cells mobility

FAK activity is increased in recruited or circulating immune cells upon enteric infection

Bioinformatics in Microbiome Analysis
廖玉潔副研究員 (群體健康科學研究所)

Metagenomics: the term metagenomics has been defined as

The study of DNA from

The study of DNA from uncultured organisms” (Jo Handelsman). A genome is the entire genetic information of one organism, whereas a metagenome is the entire genetic information of an ensemble of organisms. It is a culture-independent tool for studying bacterial, viral, fungal or eukaryotic communities and can be divided in two main categories.

http://www.seqomics.hu/index.php?option=com_content&view=article&id=44&Itemid=139

Targeted amplicon: 16S

> 97% identity : same species

RDP classifier:

Silva nags

Database (GREENGENES)

TestPrime (primer design) —> a good site for primer design

An evaluation of the accuracy and speed of metagenomics analysis tools (Scientific Reports 2016 Jan 18)

Centrifuge: (Genome Medicine)

We have built an anlystical pipeline for metagenomics analysis

KEGG profiles. (Brite KEGG). Metabolites

Metagenomics assembly

Thosands of microbial genomes shed light on interconnected biogenchemical processes in an

• 40G /sample (current cancer metagenom ~ 5G/sample)

DrVM: detect and reconstruct viral genomes from metagenomes

Simulation datasets

10X to 50X HCV: 485-2425 100-0bp paired-end HCV reads + 3.5

Human Papilloma virus

Day 2

Opportunities and Challenges of Current Immuno-oncology Landscape
林文傑助研究員 (免疫醫學中心)

Slide全換成和高承源一樣的、overview型態

Immunotherapy with SurVaxM fo ra patient with glioblastoma

IO global market

IGCG international cancer genomics consortium (25.

Oncolytic Virotherapy for Making Cold Tumors “HOT”
徐祖安研究員 (生技與藥物研究所)

改題目了！ —> Oncolytic Viruses: updates on current and promising landscapes

Several key factors contributing to ICI (CPI, checkpoint inhibitor) therapy failures

• low mutational loads and poor tumor immunogenicity

• immune suppressive micro environment

ICP34.5 deleted HSC with enhanced oncolytic, immune stimulating and anti-tumor properties RS Coffin Gene Therapy 2003, 10, p292

Use of new HSV strain JS1

deletion of ICP47

Deletion of ICP34.5

Earlier insertion of US11

Insertion f human GM-CSF

BioVex. company Feb 1999

Founders: Davis Latchman and Robert Coffin

CEO: Garett’s Beynon

Employees: 35

Financing to date: $20 millions

2011 BoVex was sold to Amgen

2015 JCO

Talimogene laherparepvec (T-VEC)

Anti-tumor response of T-VEC

2015 Oct T-VEC, Imlygic

local effect: tumor cell lysis

systemic effect: tumor-specific immune response

Oncologist cvirotherapy promoes intratumoral T cell infiltration and improves anti-PD1 immunotherapy (Cell 2107)

ORR=62%

ClinicalTrials.gov. 37 studies found for T-VEC

Study design and clinical responses

Combination f T-VEC and permsrolizuyman is effective i

n patients with low tumor CD8+ density

Future perspectives

• there is a limitation with regard to the degree of efficacy seems in the more advanced patients with extensive visceral disease

• The fact that T-VEC is injected into

Replimune, headquartered in Oxford UK and with a significant

RP1 anti-CTLA-4 and anti-PD1 were inserted into oncovirus

Experimental therapy of human gloom a by means of a genetically engineered virus mutant (Donald M Coen)

What else?

RNA viruses

PVSRIPO —> poliovirus

• Internal ribosomal entry site substitution eliminates neurovirulence in inter generic poliovirus recombinants 1996 PNAS Vol 93 pp2370-2375

• The poliovirus IRES was replaced with an IRES from human rhinovirus. THe elimination f the neuro cytopathic phenotype was achieved.

• Intergeneric poliovirus recombinants for the treatment of …

Measles virus

• development of new therapy for canine mammary cancer with recombinant measles virus Molecular Theray-Oncolytic virus

Merck Viralytics. (Coxsackievirus)

Zika virus has oncolytic activity against glioblastoma J Exp Medicine. 2017 Sep (Chheda MG)

Development and Opportunities of Antibody-based Immunotherapeutics in Mainstream Oncology 官建村副所長 (生技中心生物製藥研究所) (Duke University)

CAR-T therapy is imilar to an autologous BM transplantation

CAR therapy is at the same time cell therapy, gene therapy, and immunotherapy. It represents a radical departure from all forms of medicine in existence

Tumor antigen specific gene therapy nu gene-modified T lymphocytes

• HLA-independent

• amplification of

• 41BB —> CD137-CD3 eta??

Engineered T cells for cancer therapy. History

• expression of immunoglobulin T cell receptor chimeric molecules as functional receptors with antibody-type Rosenberg

A cure for cancer

How CAR-T therapy Is reviltiozing oncology

There ar Enoch alost 300 CAR-T clinical trials running and the first CAR-T

CRS; cytokines release

Severe side effects in selected

CS19 is an ideal tumor target

• CD19 expression is restricted to B cells and possibly follicular dendritic cells

• CD19 is not expressed on pluripotent bone marrow stem cells

• CD19 is expressed

Issues in CD19 CAR-T cell therapy

Over immune reactions (cytokines release syndromes, CRS)

Active surveillance

Anti-IL-6R

Steroid

Alternative: treats patients with lower tumor burden

CND neurotoxicity

Solution

Tissue-specific CAR-T cell activation

Lesson learned: CD19 CAR-T cell therapy

Tumor tamed by transfer of one T cell

Dusruotiuon of TET2 promotes the therapeutic efficacy of CD19-targeted T cells(CD19 escape)

1st Gen CAR

T cells died in 1 week

2nd Gen CAR

Largest challenges

CRS: to decrease toxicity (not meets to treat CRS bout to prevent it

Solid tumors (

Effector cells and target cells

EGFRvIII

Clinical development of RIT (MR1-1)

Directed to EGFRvIII

Dual-specific recombinant immunottoxin D2C7

D2C7-IT is an immunotixunb targeting both types of EGF receptor

EGFRvIII-CD3 bispecific antibody

EGFRvII murineCAR retroivurakl gebe delivery to marine T cells confers antigen-specific activityadpotive T-cell therapy with EGFRvIII mCAR T cells persistence

Rational development and characterization of humanized anti-EGFRVIII variant II chimeric antigens receptor T cells for

(NCT02209376)

• phase 1 : no CAR was observed

But T-reg was enriched

• 7×19 CAR-T

L7/CCl19-producing CAR-T cells. Improved T cell expansion land survival during in vitro

Complete regression of pre-established solid tumor

Novel strategies to enhance the efficacy of CAR-T cell therapy for aiolid tumor

— combination therapies

Bi-specific antibodies

Dynamic Interplay Between Tumor Cells and Macrophages
楊慕華副校長 (陽明大學)

Polarization of macrophages

EMT transition Lin cancer metastasis

Science 2013 342: 708 Neto et al

Hybrid EMT. Mesenchymal cell proliferates slower than epithelial cells

2014 Cancer Cell Hsu et al 26:p534

The EMT transcription factor Snail: acetates snack poteuintiae macrophage recruited to

Snail-expressing cancer cells ar also shale to polarize macrophages toward M2. (CCL2, CCl5)

MiR-21 promotes M2 polarization of macrophages

——- Epithelial plasticity in cancer metastasis

Hybrid EMT/MET

Characteristics of

Primary TAMs express both M1;M2 markers and metastatic TAMs express M2 markers

MetastatjcTAM

Metastatic TAMs promotes mesenchumal-0epithelial transition f cancer cells

JAK-STAT6 mediated M2 mTAM induct nmetastatic colonoizatino and MET

*Ruzolitinib inhibitor. (GATA3 is an important transcription factor for epithelial cell differentiation

IK35 is an IL12 family’s cytokines produced buy regulatory nit mot effector, T-cells and Paul’s a role in immune suppression

It us a diuretic protein composed of IUL12a and IL27b chains which ar e encoded by two separate genes called IL12A and EBI2

MTAMs secrete IL23

Neutralization of IL35 represses metastatic colonization

Nature Comm 2018 Lee et al

STING and cancer

Interplay between CSC nad TME

Opportunities for Small Molecules in Immuno-oncology
顏婉菁研究員 (生技與藥物研究所)

Factors to consider for success

Antibodies vs small molecule immune checkpoint inhibitors

• effective population specific to target of interest

• PK ling t1/2 (> 15-20 days)

• co-targeting PDL1 and VISTA (v-domain Is suppressor of T-cell activation)

• PDL1 and VISTA pathways ar independent immune checkpoints that negatively regulate T-cell functions\

• CA170- the first in class dual PPDL1/VISTA inhibitor

•

Antagonism of PDL1 and VISTA by CA170 ex-Vito activation of Hyman PMBMC

In Vito efficacy evaluation and effect on immune profiles

Oral bioacvailability in multiple species

B16/F1 tumors

Phase 1a trial: predicable dose exposure and T cell activatiton

RORr agnoists (retinoids acid receptor related orphan receptor gamma is a nuclear receptor of NR1 family

Modulate game expression in pathways that enhance immunity and decrease immune suppression

Acts as master

LYC-55716 is a selective RORg small molecule agonist

Ex Vivo T-cell assay

MC38 colon cancer: xenografts model

4T1 breast cancer xenografts model (very immunosuppressive cancer cell made)

Immuneprofile

Actvates IL17A and suppresses

Factors considered in tumor selection

* RORg expressing

* IO proof of concepts (TILs, mutation burden

* Tumor targets

Many molecular targeted agents easer immunomodulator functions

Imatinib also inhibits IDO

All inhibitors co-targeting Timor and tumor immune microenvirom,ent

Over-expression of Axl in tumors is associated with poor prognosis,, tumor progression , metastasis,m EMT transition and drug resistance

All serves as a negative regulator of inflammation and the anti-tumor I’mue response

BGB324 bemcentinib : first in class selective Axl inhibitor

MDA-MB-231 invasion inhibition

B6 mice

T-cell dependent inhibition of immune profiles

NSCLC. Axl1 high and PDL1 low

Divers immune regulatory effects of small molecules on tumor immune micro environment

Many small molecules have direct and indirect effects on immune cell

functions

Combination strategies wiht current checkpoint inhibitors

Translating preclinical models to clinic murine and human immune system is not comparable

Potential reasons for trial failure

• unknown MOA of IDO inhibitor I ncombination with checkpoint inhibitors

• Complex ummunoregulatory effects of small milecules

• Lack of biomakkers to monitor ummubne status for patient selection

T cel infiltration is I’portant to understand responders vs non-responders especially when targeting immune suppressive tumor microenvironment

•

Differences in trial setting small phase 2 single arm trial vs large randomized phase 3 rial

Potential reasons for trial failure

Anti cancer flavonoids are mouse selective STING agonists

(One amino acid makes a gib difference!)

New approaches for small molecules-based immunotherapy

## identifications pathways and MOA of immunosuppressive and non-immunogenicity tumor types that can only be targeted/optimized by small molecules

## Phenotypic drug discovery method

• drug screening aims to quantity a phenotype or pathway where lknpwledge of the molecular target is nor trueired

## development of new milecular clases

Synthetic antibody mimetics

Small milecules with targeting and effector funtuonof the antibody

Small meals (3-20 kDa), better solubility, tiusue penetration , stability

SyAm-Ps:bind to prostate-specific membrane antigen and to Fc-gamma I to promote proinflammatory respinses against tumor cells

Potential for development of nex generation customized immunotherappies

Mitochondrial DNA Leakage and Inflammatory Cytokines Activate Innate Immune Signaling and M2-macrophage in Tumor Microenvironment
李岳倫副研究員 (癌症研究所)

*The stress phenotypes in tumor microenvironment
• hypoxia • ROS • Genome instability • Acidosis
* Tumor microenvironment targeted therapies

Mitochondrion
• mitochondria can perform multiple cellular functions including bienergy production metabolism, Ca2+ signaling, apoptosis, and autophjagy
• Mitochondria are a major source or ROS in cells
• mitochondrial respiratory complex proteins are a major source of cellular ROS
• Miochondrial resporatory

* Mitochondrial Lon-induced oxidative stress in tumorigenesis
* High ROS level as a stress phenotype in tumor
* ROS are crucial signaling molecules of signal transduction pathways that promote proliferation , inflammatory,
* Lon overexpression induces. NF-KB and IFN pathways
* Lon overexpression induces the expression of IL6 IL1B IL4 and IL13 (NF-KB directed)
* Tumor associated inflammatory cytokines regulate macrophage function
* Increased Lon expression is involved in the differentiation and activation
* The effect of Lon-overexpressing cancer cells on macrophage
* OECM1
With Lon-overexpression or shRNA of Lon
* Lon overexpression —> mitochondrial DNA —> STING, IFN, NF-KB
* Innate immunity is involved STING-TBK1-IRF3 in HSC3
* Cancer Research (2016) STING promotes the growth of tumors characterized
* KO STING (in HSC3??? )decreases TBK1, IRF3/7, IDO1/PDL1

Taiwan Cancer Moonshot: Pathway to Next Generation Cancer Precision Medicine
陳玉如所長 (中央研院化學研究所)

–Protein network critical regulation in cellular function and diseases
• Abnormal protein network is often the cause of disease initiation and progression
• Substrat, site-specific PTM regulation?
• Pathways crosstalk?
• Heterogeneity at individual patient level

–Mass spectrometry-based strategies: membrane proteome and modification

–New proteomics strategies or membrane proteome and post-translational modification
Membrane proteomics, phosphorylation, nitrosylation + others, glycosylation

–Application of proteomics strategies for delineation of disease/biology mechanism

–Nanoprobe-based affinity mass
Revised chemistry for phosphoproteomics by immobialized metal affinity chromatogranphy (IMAC)

–Ph / acid controlled IMAC 90% purification specificity and recovery

–Sequencing fractionation by IMAC-stage tip (Ti 4+, Fe 3+ Ga3+)

–Mass sepctrometry revealed dynamic interplay of phosphorylation and O-Glunacylation to switch B cell activation apoptosis. (Kudos-I Lin, Na Comm 2016)

– Lsp1 dynastic phosphorylation and O-GlcNacylation of Lsp1 switches B-cell activation and apoptosis

– Quantitative depiction of precise in biology Stoichoimetry

Phosphorylation stoichiometry is it significant

Two-fold regulation of suite stoichiometry could result from either fractional occupancy changes of 10 to 20% c=or 50 to 100% which likely represent

Are we able to differentiate changes in eithe rprotien or phosphorylation stoichiometry??

Example for phosphorylation stoichiometry measurement

The measurement of phosphorylation of

Identifying drug-resultant target through phosphoproteomic network of EGFRVIII and CK2 substrates

On the comparison between the TKI-sensitive and resistant lung cancer cell
More dramatic chang at phosphorylation level : in the resultant lung cance cell, the phosphorylation HMGA1 KD could reverse drug resistance in NSCLC PTM is important for drug resistance

Dynamic stoichiometry of EGFRVIII signaling pathway

———————-
Precious biology

An informatics-assisted mass spectrometry approach for personalized timmues membrane protein is

STOML2 as a noninvasive serological biomarker candidate fo prognosis and early CRC diagnosis

1452 origin were identified

3-protein candidates for early detection f gastric cancer. (197 protein membrane proteins)

Cancer Moonshot

US NCI 2006. Tissue Proteogenomics

CRC Nature 2014.

Proteomics identified new subtypes in colorectal cancer stage III,.. new molecular subtype

MOU signed in 2015 July
Cancer Moonshot announced by Obama 2016 Jan
VP Biden announced international al cancer Moonshot 2016, Sept)
Cancer Moonshot was included in national policy program (2016, nov) (生醫產業推動方案

2016 Taipei HUPO

International cancer proteogenome consortium

Genetic background and environmental factors contribute to unique feature of cancers in Taiwan/Asia

NSCLS

Early stage patients (n=200)
Late stage patients (n=200)

First high multi-om is atlas of personalized Taiwanese cancer cohort

Lung cancer n=400 breast cancer n=400
CRC n=400

Acre

Which platform can provide biological content to address. The unment clinical needs]]proteomics > 10,000
Phosphpoproteimics > 26000 phosphorylation sites

Most proteins in NSCLC pathways (94%) were identified

569 kinases were quantified in NSCLC tissues

Identify low abundant protein tyrosine phosphatases

Does gene subtype accurately describe a patient at the (phosphatases)

Allied specific expression profiling in lung cancer

Personalized profile in NSCLC pathway

39 SNV of somatic mutation identified in 44 patients

Night mutation rate in Asioam female (58%)
Sensitive to TKI with Del 19 and L858R mutation develop resistance within 12 moths

Personalized proteogenomic atlas revealed differential activation of signaling pathway

Gene X
Germinline mutation
Up-regulated protein level in 90% patient

X signaling and EGFRVIII-pathway (243 proteins0
Differential activation in NSCLC subtype

Degradation of extra cellular matrix

B cell receptor signaling by interleulinw

M

Taiwan protein project (2016-2019)
Applying state of the art proteogenomics to rapidly identify unique targets and pathways of cancer for detection and intervention

Targeting MCT-1/IL-6/IL-6R Signaling Inhibits EMT Progression, Cancer Stemness and M2 Macrophage Polarization in Aggressive Breast Cancer 徐欣伶副研究員 (分子與基因醫學研究所)

MCT1DENR-MCT1 heterodimer promotes …

PUA domain a highly conserved motif in …

Translational control of cancer (cancer translatome)

MCT1 abundance in intra-ducal and invasive breast carcinoma (IHC staining)

MCT1 overexpression associates with worse clinical outcomes indifferent type of breast cancer

MCT1 induces normal breast cell proliferation and causes malignant Alina morph Jolene’s is

CD163 as M2 macrophage marker

In vitro THP1 polarization M2 marker Arginase 1 , IL10?

qRT-PCR confirmed by using CD163, CD206 primers

MCT1 stimulates MCP1 GMCSF and IL6 secretion cytokine array. <— highly likely to involve M2 differentiation

Tocilizuman (Actemra) a humanized recombinant IL6R mAb

Discussion Session

Time	Topics	Speakers
13:30~13:40	Opening Remarks 梁賡義院長
Microbiome		Moderator	蔡世峯處長
13:40~14:25	Emerging Trends and Opportunities for Microbiota Research	高承源副研究員 (免疫醫學中心)
14:25~15:10	Fecal Microbiota Transplantation (FMT) for Clostridium Difficile Infection and Other Diseases	邱政洵教授 (林口長庚醫院兒童感染科)
15:10~15:55	Taiwan FMT Expert Consensus	吳俊穎主任 (臺北榮民總醫院轉譯研究科)
15:55~16:20	Break
16:20~16:50	Gut-brain Axis: a Fundamental Mechanism Modulating Alzheimer’s Progression	莊志立研究員 (分子與基因醫學研究所)
16:50~17:20	Bioinformatics in Microbiome Analysis	廖玉潔副研究員 (群體健康科學研究所)
17:20~18:00	Discussion Session
18:00~	Dinner

107年6月22日 (週五)

Time	Topics	Speakers
Cancer Immunology I		Moderator	司徒惠康副院長
09:00~09:45	Opportunities and Challenges of Current Immuno-oncology Landscape	林文傑助研究員 (免疫醫學中心)
09:45~10:20	Oncolytic Virotherapy for Making Cold Tumors “HOT”	徐祖安研究員 (生技與藥物研究所)
10:20~10:30	Break


10:30~11:15	Development and Opportunities of Antibody-based Immunotherap eutics in Mainstream Oncology	官建村副所長 (生技中心生物製藥研究所)
11:15~12:00	Dynamic Interplay Between Tumor Cells and Macrophages	楊慕華副校長 (陽明大學)
12:00~13:30	Discussion Session & Lunch
Cancer Immunology II		Moderator	施修明所長
13:30~14:00	Opportunities for Small Molecules in Immuno-oncology	顏婉菁研究員 (生技與藥物研究所)
14:00~14:30	Mitochondrial DNA Leakage and Inflammatory Cytokines Activate Innate Immune Signaling and M2-macrophage in Tumor Microenvironment	李岳倫副研究員 (癌症研究所)
14:30~15:15	Taiwan Cancer Moonshot: Pathway to Next Generation Cancer Precision Medicine	陳玉如所長 (中央研院化學研究所)
15:15~15:45	Targeting MCT-1/IL-6/IL-6R Signaling Inhibits EMT Progression, Cancer Stemness and M2 Macrophage Polarization in Aggressive Breast Cancer	徐欣伶副研究員 (分子與基因醫學研究所)
15:45~	Discussion Session

Day 2

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