Non-small cell lung cancer (NSCLC) is the most common type of lung cancer in humans. Some patients with NSCLC receive a therapy called immune checkpoint blockade (ICB) that helps kill cancer cells by reinvigorating a subset of immune cells called T cells, which are “exhausted” and have stopped working. However, only about 35 percent of NSCLC patients respond to ICB therapy. Stefani Spranger’s lab at the MIT Department of Biology explores the mechanisms behind this resistance, with the goal of inspiring new therapies to better treat NSCLC patients. In a new study published on Oct. 29 in Science Immunology, a team led by Spranger lab postdoc Brendan Horton revealed what causes T cells to be non-responsive to ICB — and suggests a possible solution.
Scientists have long thought that the conditions within a tumor were responsible for determining when T cells stop working and become exhausted after being overstimulated or working for too long to fight a tumor. That’s why physicians prescribe ICB to treat cancer — ICB can invigorate the exhausted T cells within a tumor. However, Horton’s new experiments show that some ICB-resistant T cells stop working before they even enter the tumor. These T cells are not actually exhausted, but rather they become dysfunctional due to changes in gene expression that arise early during the activation of a T cell, which occurs in lymph nodes. Once activated, T cells differentiate into certain functional states, which are distinguishable by their unique gene expression patterns.
The notion that the dysfunctional state that leads to ICB resistance arises before T cells enter the tumor is quite novel, says Spranger, the Howard S. and Linda B. Stern Career Development Professor, a member of the Koch Institute for Integrative Cancer Research, and the study’s senior author.
“We show that this state is actually a preset condition, and that the T cells are already non-responsive to therapy before they enter the tumor,” she says. As a result, she explains, ICB therapies that work by reinvigorating exhausted T cells within the tumor are less likely to be effective. This suggests that combining ICB with other forms of immunotherapy that target T cells differently might be a more effective approach to help the immune system combat this subset of lung cancer.
In order to determine why some tumors are resistant to ICB, Horton and the research team studied T cells in murine models of NSCLC. The researchers sequenced messenger RNA from the responsive and non-responsive T cells in order to identify any differences between the T cells. Supported in part by the Koch Institute Frontier Research Program, they used a technique called Seq-Well, developed in the lab of fellow Koch Institute member J. Christopher Love, the Raymond A. (1921) and Helen E. St. Laurent Professor of Chemical Engineering and a co-author of the study. The technique allows for the rapid gene expression profiling of single cells, which permitted Spranger and Horton to get a very granular look at the gene expression patterns of the T cells they were studying.
Seq-Well revealed distinct patterns of gene expression between the responsive and non-responsive T cells. These differences, which are determined when the T cells assume their specialized functional states, may be the underlying cause of ICB resistance.
Now that Horton and his colleagues had a possible explanation for why some T cells did not respond to ICB, they decided to see if they could help the ICB-resistant T cells kill the tumor cells. When analyzing the gene expression patterns of the non-responsive T cells, the researchers had noticed that these T cells had a lower expression of receptors for certain cytokines, small proteins that control immune system activity. To counteract this, the researchers treated lung tumors in murine models with extra cytokines. As a result, the previously non-responsive T cells were then able to fight the tumors — meaning that the cytokine therapy prevented, and potentially even reversed, the dysfunctionality.
Administering cytokine therapy to human patients is not currently safe, because cytokines can cause serious side effects as well as a reaction called a “cytokine storm,” which can produce severe fevers, inflammation, fatigue, and nausea. However, there are ongoing efforts to figure out how to safely administer cytokines to specific tumors. In the future, Spranger and Horton suspect that cytokine therapy could be used in combination with ICB.
“This is potentially something that could be translated into a therapeutic that could increase the therapy response rate in non-small cell lung cancer,” Horton says.
Spranger agrees that this work will help researchers develop more innovative cancer therapies, especially because researchers have historically focused on T cell exhaustion rather than the earlier role that T cell functional states might play in cancer.
“If T cells are rendered dysfunctional early on, ICB is not going to be effective, and we need to think outside the box,” she says. “There’s more evidence, and other labs are now showing this as well, that the functional state of the T cell actually matters quite substantially in cancer therapies.” To Spranger, this means that cytokine therapy “might be a therapeutic avenue” for NSCLC patients beyond ICB.
Jeffrey Bluestone, the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology at the University of California-San Francisco, who was not involved with the paper, agrees. “The study provides a potential opportunity to ‘rescue’ immunity in the NSCLC non-responder patients with appropriate combination therapies,” he says.
This research was funded by the Pew-Stewart Scholars for Cancer Research, the Ludwig Center for Molecular Oncology, the Koch Institute Frontier Research Program through the Kathy and Curt Mable Cancer Research Fund, and the National Cancer Institute.
Original Source: news.mit.edu
Lash Extension Specialists in NJ Offer Free Consultations for Eyelash Services
As published by Digitaljournal.com, the details about NJ Lash Extensions Artist Offers Free Consultation with Eyelash Services have future implications.
In 2018, Eyelash Extensions were searched for thousands of times on 883,000. In Today, 2.2M searches are made per month for the same term, attracting a wide range of demographics, including 18 to 34-year-old women.
Ash Santiago’s job as an esthetician involves a lot of communication. In it, she wants to help clients establish long-term relationships and achieve their desired looks.
Read a clipping of the story below
New York – In 2018, US-based Google searches for the term Eyelash Extensions were trending and averaging about 883,000 per month. Fast forward to today and searches for the same term are now averaging 2.2M searches per month. Eyelash extensions have sprung their own industry and continue to attract a wide demographic ranging from 18 to 34-year-old women. Lash studios have started to pop up across the tri-state area prompting many women to research where to find the best place for eyelash extensions in NJ.
Ash Santiago is a beauty specialist in New Jersey offering high-quality and stylish eyelash extensions, professional makeup, waxing, and facial services. Her premiere eyelash extension services have been touted as one of the best lash extension services in New Jersey.
Here Are Some Aftercare Tips Shared by an Expert Eyelash Artist and Esthetician
This commentary is by Cassandra Thomas of vaf.io
Aftercare is essential for the longevity and health of your eyelash extensions.
Following your eyelash extensions, you should clean them twice a day and brush them twice a day with a spoolie brush. You should also completely dry wet lashes. The use of makeup that is oily or salty should be avoided.
Read more about Expert Lash Artist and Esthetician Shares Aftercare Tips for Longer Lasting Eyelash Extensions
New York – There’s a secret to perfect eyelash extensions that last. Expert lash artist and a popular provider of best place for eyelash extensions in nj shares aftercare tips to ensure your eyelash extensions last longer and stay healthier.
According to Santiago, important aftercare tips for eyelash extensions include cleaning the lashes at least twice a day using a quality cleanser, brushing the lashes using a spoolie brush, and completely drying wet lashes. Aftercare habits to keep lashes clean help avoid infections, and extend the life of lash extensions.
Click to get the full scoop: Benzinga.com
NJ Lash Extensions Studio Introduces Luxurious Lashes With More Volume for Eyelashes
The Latest Update about NJ Lash Extensions Studio Introduces Luxurious Lashes for More Eyelash Volume
Luxurious eyelash extensions that provide more volume are being offered at a popular lash studio in NJ. In addition to making the lash line more visible, the extensions make it appear thicker and thicker.
The studio is offering a full set of eyelash extensions at a special promotional price. The lash artist applies the extensions with precision to create a masterpiece that frames the eyes perfectly.
Read this paragraph from the article:
New York – Everyone adores beautiful eyes. NJ’s popular lash studio announces the latest in eyelash extensions in New Jersey. The studio now offers clients a full-set of luxurious eyelash extensions that not only make the eyes beautiful but make the lash line thicker and more voluminous. The full set uses cutting-edge techniques that further enhance lash extensions for a glamourous look that commands attention.
“It is a fact that lash extensions make the eyes appear brighter without wearing any makeup,” said Santiago. “I believe that looking great is the best way to boost one’s confidence.” The lash studio uses only the highest quality hypoallergenic and cruelty-free products. Thus, customers have peace-of-mind that their lashes are safe, easier to maintain and longer lasting.
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