The development of immune checkpoint blockers (ICB) has considerably changed the therapeutic armamentarium for the management of cancer. Blocking the PD-1/PD-L1 axis interaction has demonstrated remarkable anti-cancer activity and has led to approval of anti-PD-1/PD-L1 drugs in several solid tumors. However, most patients receiving PD(L)-1 blockers do not derive clinical benefit. Therefore, there is a crucial need to decipher mechanisms underlying sensitivity / resistance to cancer immunotherapies which can ultimately lead to the identification of novel therapeutic targets.
Through a collaborative work (with Institut Bergonié) using the GeoMx-DSP technology platform (NanostringTM) and the GeoMx® Immune Pathways Panel, and aiming at delineating biological pathways involved in resistance / sensitivity of NSCLC to anti-PD-(L)1-based immunotherapies, we investigated the spatial transcriptomic profile of tumor samples collected before treatment onset of responder (and non-responder patients. Tumor- and Stroma-specific gene expression was analyzed through the application of morphology markers including PanCytoKeratin (PanCK) for tumor cells and CD45 for immune cells.
Figure 1. GeoMx workflow analysis. Tissues were incubated with the GeoMx® Immune Pathways Panel probes and stained with the morphology markers CD45 and PanCytokeratin (PanCK). Regions of interest were drawn in mixed tumor/stroma areas and were then segmented in Tumor (PanCK) and Stroma (PanCK-) compartments. Expression of 78 protein-coding genes related to tumor microenvironment profiling were finally analyzed on the Nanostring nCounter platform.
Unsupervised data clustering evidenced a strong stratification of responder and non-responder patients with data collected from the stroma compartment. Using this dataset, we performed a differential gene expression analysis between responders and patients with a progressive disease (PD). This analysis allowed to reveal key determinants of response to ICB in NSCLC patients whose some genes involved in immune escape, e.g. Ctla4, Arg1, Ido1, were enriched in PD patients.
Figure 2. Analysis of the determinants of the ICI response. Sixteen tumor samples from NSCLC patients (8 responders – OR and 8 non-responders – PD) were analyzed on the GeoMx® DSP using the GeoMx® Immune pathways panel (11-12 ROIs per patients). (A-B) Heatmap representations of the tumor (A) and stroma (B) specific gene expression. (C) Differential gene expression analysis of the stroma-specific gene expression from responders and non-responders patients . OR stands for Objective Response and PD for Progressive Disease.
Besides revealing known and novel markers underlying sensitivity to ICB in NSCLC patients, this novel dataset illustrates the key benefit of the spatial transcriptomic approach that can be conducted with a limited and target panel (e.g. immune pathway) or with a more comprehensive approach using Cancer or Whole Transcriptome Atlas panels (1800 and 18000 genes, respectively).
Learn more about our platform in spatial transcriptomics
Donovan AWvZGfedrekvhPiK 5 21 2022 priligy united states There are no words to comfort enough
11 rose by 77 bcf to 3 buy priligy usa Is 143 over 95 bad blood pressure
Their specific target the DPP 4 enzyme also known as CD26 16 36 is a type II transmembrane glycoprotein that exists as a soluble form in body fluids 35 and which is ubiquitously expressed on the surface of a big variety of cells 29 37 cytotec online india
What she became in her last years was something quite different a disciple of spiritual healing, a patron of Tibetan monks, a believer that exposure to controlled sound and colour could rearrange the body s aberrant molecules buying unprescribed clomid
Farmacie online sicure: Farma Prodotti – farmacia online senza ricetta
acquisto farmaci con ricetta
Farmacia online miglior prezzo: Cialis generico – acquisto farmaci con ricetta
cialis farmacia senza ricetta [url=https://farmasilditaly.com/#]viagra online siti sicuri[/url] viagra 100 mg prezzo in farmacia
https://farmaprodotti.shop/# farmacia online piГ№ conveniente
farmacie online sicure
https://phtaya.tech/# The casino atmosphere is thrilling and energetic.
Many casinos offer luxurious amenities and services.
Some casinos have luxurious spa facilities.: phmacao casino – phmacao com login
https://jugabet.xyz/# La mГєsica acompaГ±a la experiencia de juego.
Entertainment shows are common in casinos.
taya777 login [url=http://taya777.icu/#]taya777 register login[/url] Responsible gaming initiatives are promoted actively.
Players often share tips and strategies. https://taya777.icu/# Gambling regulations are strictly enforced in casinos.
La seguridad es prioridad en los casinos.: winchile casino – win chile
https://phmacao.life/# The thrill of winning keeps players engaged.
The Philippines offers a rich gaming culture.
The Philippines has several world-class integrated resorts. https://phmacao.life/# Players must be at least 21 years old.
Slot machines attract players with big jackpots.: phtaya.tech – phtaya
https://taya365.art/# The Philippines offers a rich gaming culture.
Casinos often host special holiday promotions.
phmacao com [url=https://phmacao.life/#]phmacao com[/url] The ambiance is designed to excite players.
Gambling can be a social activity here.: taya777 – taya777
Some casinos feature themed gaming areas. http://phmacao.life/# Players enjoy both fun and excitement in casinos.
https://phtaya.tech/# The Philippines offers a rich gaming culture.
The Philippines has several world-class integrated resorts.
п»їLos casinos en Chile son muy populares.: jugabet – jugabet.xyz
https://phmacao.life/# Many casinos host charity events and fundraisers.
Players often share tips and strategies.
The Philippines offers a rich gaming culture. https://taya365.art/# Players enjoy a variety of table games.
Live music events often accompany gaming nights.: phmacao.life – phmacao casino
phmacao casino [url=http://phmacao.life/#]phmacao club[/url] Resorts provide both gaming and relaxation options.
https://taya365.art/# Live music events often accompany gaming nights.
Loyalty programs reward regular customers generously.
Players enjoy both fun and excitement in casinos.: taya365 – taya365 com login
The Philippines has a vibrant nightlife scene. http://taya365.art/# Gambling regulations are strictly enforced in casinos.
Gaming regulations are overseen by PAGCOR.: phtaya login – phtaya.tech
winchile [url=http://winchile.pro/#]winchile casino[/url] Los pagos son rГЎpidos y seguros.
http://phtaya.tech/# Many casinos have beautiful ocean views.
Live music events often accompany gaming nights.
High rollers receive exclusive treatment and bonuses.: taya365 com login – taya365
Some casinos have luxurious spa facilities.: taya777 register login – taya777
https://phtaya.tech/# The casino atmosphere is thrilling and energetic.
Players can enjoy high-stakes betting options.
Players enjoy a variety of table games. http://winchile.pro/# La diversiГіn nunca se detiene en los casinos.
phmacao club [url=https://phmacao.life/#]phmacao club[/url] п»їCasinos in the Philippines are highly popular.
http://winchile.pro/# Muchos casinos tienen salas de bingo.
Many casinos provide shuttle services for guests.
The casino experience is memorable and unique.: taya365 login – taya365.art
http://taya777.icu/# Casino visits are a popular tourist attraction.
Players can enjoy high-stakes betting options.
Manila is home to many large casinos.: taya365 login – taya365
Slot machines feature various exciting themes. http://taya365.art/# Casino visits are a popular tourist attraction.
Gambling can be a social activity here.: taya365.art – taya365 login
http://winchile.pro/# La variedad de juegos es impresionante.
The casino scene is constantly evolving.
taya777 [url=https://taya777.icu/#]taya777 app[/url] Many casinos provide shuttle services for guests.
http://taya365.art/# Manila is home to many large casinos.
Entertainment shows are common in casinos.
La historia del juego en Chile es rica.: winchile casino – winchile.pro
http://taya365.art/# Live dealer games enhance the casino experience.
The casino industry supports local economies significantly.
Las promociones de fin de semana son populares.: winchile casino – winchile.pro
taya777 register login [url=http://taya777.icu/#]taya777 login[/url] Gambling regulations are strictly enforced in casinos.
https://taya777.icu/# The thrill of winning keeps players engaged.
Poker rooms host exciting tournaments regularly.
Muchos casinos ofrecen restaurantes y bares.: jugabet.xyz – jugabet.xyz
http://taya777.icu/# Game rules can vary between casinos.
The thrill of winning keeps players engaged.
Live music events often accompany gaming nights.: taya777.icu – taya777
Players enjoy a variety of table games. http://taya777.icu/# Slot machines feature various exciting themes.
https://phmacao.life/# Casino promotions draw in new players frequently.
Many casinos offer luxurious amenities and services.
taya365 login [url=http://taya365.art/#]taya365.art[/url] The Philippines has several world-class integrated resorts.
Many casinos provide shuttle services for guests.: taya777.icu – taya777 register login
https://taya365.art/# Casinos offer delicious dining options on-site.
Players enjoy both fun and excitement in casinos.
Hay casinos en Santiago y ViГ±a del Mar.: winchile – winchile.pro
The Philippines has a vibrant nightlife scene.: taya365 login – taya365 login
https://jugabet.xyz/# Las promociones atraen nuevos jugadores diariamente.
The Philippines has a vibrant nightlife scene.
jugabet chile [url=https://jugabet.xyz/#]jugabet chile[/url] Las mГЎquinas tragamonedas tienen temГЎticas diversas.
Promotions are advertised through social media channels.: phmacao com login – phmacao com
Loyalty programs reward regular customers generously.: phtaya login – phtaya login
http://taya777.icu/# Poker rooms host exciting tournaments regularly.
Visitors come from around the world to play.
The casino experience is memorable and unique. https://taya777.icu/# Players enjoy both fun and excitement in casinos.
http://taya365.art/# The ambiance is designed to excite players.
Slot machines attract players with big jackpots.
Los jugadores pueden disfrutar desde casa.: winchile.pro – win chile
phtaya [url=http://phtaya.tech/#]phtaya casino[/url] Resorts provide both gaming and relaxation options.
https://jugabet.xyz/# Las apuestas deportivas tambiГ©n son populares.
Entertainment shows are common in casinos.
Many casinos have beautiful ocean views.: taya365 login – taya365 com login
Online gaming is also growing in popularity.: taya365 com login – taya365 login
http://taya365.art/# Many casinos provide shuttle services for guests.
Poker rooms host exciting tournaments regularly.
Some casinos feature themed gaming areas.: taya777 register login – taya777.icu
http://winchile.pro/# La ruleta es un juego emocionante aquГ.
The Philippines has several world-class integrated resorts.
winchile casino [url=http://winchile.pro/#]winchile casino[/url] Los casinos organizan eventos especiales regularmente.
Players enjoy a variety of table games. http://taya365.art/# Some casinos feature themed gaming areas.
Game rules can vary between casinos.: phtaya login – phtaya.tech
Casinos offer delicious dining options on-site.: phmacao com – phmacao club
http://taya777.icu/# Cashless gaming options are becoming popular.
Players must be at least 21 years old.
promo code for canadian pharmacy meds https://megaindiapharm.shop/# Online medicine order
rxpharmacycoupons https://easycanadianpharm.com/# canadian pharmacy antibiotics
easy canadian pharm: easy canadian pharm – canadian mail order pharmacy
legit non prescription pharmacies https://easycanadianpharm.com/# canadian pharmacy 365
reputable indian pharmacies [url=https://megaindiapharm.shop/#]MegaIndiaPharm[/url] Mega India Pharm
best canadian pharmacy no prescription https://megaindiapharm.com/# Mega India Pharm
easy canadian pharm: easy canadian pharm – easy canadian pharm
online pharmacy discount code https://easycanadianpharm.shop/# ed drugs online from canada
no prescription required pharmacy http://xxlmexicanpharm.com/# xxl mexican pharm
Cheapest online pharmacy: Best online pharmacy – family pharmacy
discount drug mart pharmacy [url=http://discountdrugmart.pro/#]drug mart[/url] discount drug pharmacy
xxl mexican pharm: xxl mexican pharm – reputable mexican pharmacies online
online pharmacy discount code http://familypharmacy.company/# Cheapest online pharmacy
canadian pharmacy world coupon http://discountdrugmart.pro/# discount drugs
Online pharmacy USA: family pharmacy – family pharmacy