* . *
  • About
  • Advertise
  • Privacy & Policy
  • Contact
Sunday, July 6, 2025
Earth-News
  • Home
  • Business
  • Entertainment
    Magicians and Battlebots light up Las Vegas entertainment scene – KSNV

    Magicians and Battlebots Take Las Vegas Entertainment by Storm

    Max-Matching Entertainments & Longhua District form partnership for new entertainment complex – Blooloop

    Max-Matching Entertainments and Longhua District Unite to Launch Thrilling New Entertainment Complex

    Kennedy Publishing, MGA Entertainment Launch Yummiland Magazine – License Global

    Kennedy Publishing, MGA Entertainment Launch Yummiland Magazine – License Global

    MAY HER SOUL REST IN PEACE 🙏 Veteran entertainment columnist and talent manager Lolit Solis has passed away. She was 78 years old. https://tinyurl.com/6kumarkx | LatestChika.com – Facebook

    Beloved Entertainment Icon Lolit Solis Passes Away at 78 – A Life Remembered with Love and Respect 🙏

    Neil Young Plays Rare Full-Band ‘Ambulance Blues’ With The Chrome Hearts – Yahoo

    Neil Young Stuns Fans with Rare Full-Band Performance of ‘Ambulance Blues’ Alongside The Chrome Hearts

    BTS Announce Their Big Return and Yes, They Already Have Some Major Plans in the Works – Yahoo

    BTS Announce Their Big Return and Yes, They Already Have Some Major Plans in the Works – Yahoo

  • General
  • Health
  • News

    Cracking the Code: Why China’s Economic Challenges Aren’t Shaking Markets, Unlike America’s” – Bloomberg

    Trump’s Narrow Window to Spread the Truth About Harris

    Trump’s Narrow Window to Spread the Truth About Harris

    Israel-Gaza war live updates: Hamas leader Ismail Haniyeh assassinated in Iran, group says

    Israel-Gaza war live updates: Hamas leader Ismail Haniyeh assassinated in Iran, group says

    PAP Boss to Niger Delta Youths, Stay Away from the Protest

    PAP Boss to Niger Delta Youths, Stay Away from the Protest

    Court Restricts Protests In Lagos To Freedom, Peace Park

    Court Restricts Protests In Lagos To Freedom, Peace Park

    Fans React to Jazz Jennings’ Inspiring Weight Loss Journey

    Fans React to Jazz Jennings’ Inspiring Weight Loss Journey

    Trending Tags

    • Trump Inauguration
    • United Stated
    • White House
    • Market Stories
    • Election Results
  • Science
  • Sports
  • Technology
    EIFO invests $5 million in D3, the Ukraine-focused defence technology venture fund – sUAS News

    EIFO Commits $5 Million to Boost Ukraine-Focused Defense Tech Fund D3

    New Technology for Water Efficiency and Working with Mexico on Screwworm – AG INFORMATION NETWORK OF THE WEST

    Revolutionary Water Efficiency Technology and Cross-Border Collaboration to Defeat Screwworm

    Environmental cognitive distance, R&D capability distance, and supply chain green technology innovation – Nature

    Bridging Gaps: How Environmental and R&D Differences Drive Green Technology Innovation in Supply Chains

    LG Innotek CEO Moon Hyuksoo: “Our Next-gen Substrate Technology Will Change the Industry Paradigm” – TechPowerUp

    LG Innotek CEO Moon Hyuksoo: “Our Next-Gen Substrate Technology Will Revolutionize the Industry” Revolutionizing the Future: LG Innotek’s CEO Unveils Game-Changing Next-Gen Substrate Technology

    Inspira Technologies Secures Landmark $22.5M Deal: Major Revenue Breakthrough After FDA Clearance – Stock Titan

    Inspira Technologies Secures Landmark $22.5M Deal: Major Revenue Breakthrough After FDA Clearance – Stock Titan

    Meiwu Technology Company Limited and Shenzhen Zhinuo – GlobeNewswire

    Meiwu Technology Company Limited and Shenzhen Zhinuo – GlobeNewswire

    Trending Tags

    • Nintendo Switch
    • CES 2017
    • Playstation 4 Pro
    • Mark Zuckerberg
No Result
View All Result
  • Home
  • Business
  • Entertainment
    Magicians and Battlebots light up Las Vegas entertainment scene – KSNV

    Magicians and Battlebots Take Las Vegas Entertainment by Storm

    Max-Matching Entertainments & Longhua District form partnership for new entertainment complex – Blooloop

    Max-Matching Entertainments and Longhua District Unite to Launch Thrilling New Entertainment Complex

    Kennedy Publishing, MGA Entertainment Launch Yummiland Magazine – License Global

    Kennedy Publishing, MGA Entertainment Launch Yummiland Magazine – License Global

    MAY HER SOUL REST IN PEACE 🙏 Veteran entertainment columnist and talent manager Lolit Solis has passed away. She was 78 years old. https://tinyurl.com/6kumarkx | LatestChika.com – Facebook

    Beloved Entertainment Icon Lolit Solis Passes Away at 78 – A Life Remembered with Love and Respect 🙏

    Neil Young Plays Rare Full-Band ‘Ambulance Blues’ With The Chrome Hearts – Yahoo

    Neil Young Stuns Fans with Rare Full-Band Performance of ‘Ambulance Blues’ Alongside The Chrome Hearts

    BTS Announce Their Big Return and Yes, They Already Have Some Major Plans in the Works – Yahoo

    BTS Announce Their Big Return and Yes, They Already Have Some Major Plans in the Works – Yahoo

  • General
  • Health
  • News

    Cracking the Code: Why China’s Economic Challenges Aren’t Shaking Markets, Unlike America’s” – Bloomberg

    Trump’s Narrow Window to Spread the Truth About Harris

    Trump’s Narrow Window to Spread the Truth About Harris

    Israel-Gaza war live updates: Hamas leader Ismail Haniyeh assassinated in Iran, group says

    Israel-Gaza war live updates: Hamas leader Ismail Haniyeh assassinated in Iran, group says

    PAP Boss to Niger Delta Youths, Stay Away from the Protest

    PAP Boss to Niger Delta Youths, Stay Away from the Protest

    Court Restricts Protests In Lagos To Freedom, Peace Park

    Court Restricts Protests In Lagos To Freedom, Peace Park

    Fans React to Jazz Jennings’ Inspiring Weight Loss Journey

    Fans React to Jazz Jennings’ Inspiring Weight Loss Journey

    Trending Tags

    • Trump Inauguration
    • United Stated
    • White House
    • Market Stories
    • Election Results
  • Science
  • Sports
  • Technology
    EIFO invests $5 million in D3, the Ukraine-focused defence technology venture fund – sUAS News

    EIFO Commits $5 Million to Boost Ukraine-Focused Defense Tech Fund D3

    New Technology for Water Efficiency and Working with Mexico on Screwworm – AG INFORMATION NETWORK OF THE WEST

    Revolutionary Water Efficiency Technology and Cross-Border Collaboration to Defeat Screwworm

    Environmental cognitive distance, R&D capability distance, and supply chain green technology innovation – Nature

    Bridging Gaps: How Environmental and R&D Differences Drive Green Technology Innovation in Supply Chains

    LG Innotek CEO Moon Hyuksoo: “Our Next-gen Substrate Technology Will Change the Industry Paradigm” – TechPowerUp

    LG Innotek CEO Moon Hyuksoo: “Our Next-Gen Substrate Technology Will Revolutionize the Industry” Revolutionizing the Future: LG Innotek’s CEO Unveils Game-Changing Next-Gen Substrate Technology

    Inspira Technologies Secures Landmark $22.5M Deal: Major Revenue Breakthrough After FDA Clearance – Stock Titan

    Inspira Technologies Secures Landmark $22.5M Deal: Major Revenue Breakthrough After FDA Clearance – Stock Titan

    Meiwu Technology Company Limited and Shenzhen Zhinuo – GlobeNewswire

    Meiwu Technology Company Limited and Shenzhen Zhinuo – GlobeNewswire

    Trending Tags

    • Nintendo Switch
    • CES 2017
    • Playstation 4 Pro
    • Mark Zuckerberg
No Result
View All Result
Earth-News
No Result
View All Result
Home Science

Study explains why certain immunotherapies don’t always work as predicted

September 18, 2023
in Science
Study explains why certain immunotherapies don’t always work as predicted
Share on FacebookShare on Twitter

Study explains why certain immunotherapies don't always work as predicted

Caption:In this colon tumor, which has a mutation that gives it a high degree of DNA mismatch repair deficiency, T cells (labeled black, green, and red) have accumulated primarily in the supportive tissues (pink regions), while very few have infiltrated tumor cells (islands surrounded by the supportive tissues). Credit: Courtesy of the researchers

This block is broken or missing. You may be missing content or you might need to enable the original module.

Cancer drugs known as checkpoint blockade inhibitors have proven effective for some cancer patients. These drugs work by taking the brakes off the body’s T cell response, stimulating those immune cells to destroy tumors.

Some studies have shown that these drugs work better in patients whose tumors have a very large number of mutated proteins, which scientists believe is because those proteins offer plentiful targets for T cells to attack. However, for at least 50 percent of patients whose tumors show a high mutational burden, checkpoint blockade inhibitors don’t work at all.

A new study from MIT reveals a possible explanation for why that is. In a study of mice, the researchers found that measuring the diversity of mutations within a tumor generated much more accurate predictions of whether the treatment would succeed than measuring the overall number of mutations.

If validated in clinical trials, this information could help doctors to better determine which patients will benefit from checkpoint blockade inhibitors.

“While very powerful in the right settings, immune checkpoint therapies are not effective for all cancer patients. This work makes clear the role of genetic heterogeneity in cancer in determining the effectiveness of these treatments,” says Tyler Jacks, the David H. Koch Professor of Biology and a member of MIT’s Koch Institute for Cancer Research.

Jacks; Peter Westcott, a former MIT postdoc in the Jacks lab who is now an assistant professor at Cold Spring Harbor Laboratory; and Isidro Cortes-Ciriano, a research group leader at EMBL’s European Bioinformatics Institute (EMBL-EBI), are the senior authors of the paper, which appears today in Nature Genetics.

A diversity of mutations

Across all types of cancer, a small percentage of tumors have what is called a high tumor mutational burden (TMB), meaning they have a very large number of mutations in each cell. A subset of these tumors has defects related to DNA repair, most commonly in a repair system known as DNA mismatch repair.

Because these tumors have so many mutated proteins, they are believed to be good candidates for immunotherapy treatment, as they offer a plethora of potential targets for T cells to attack. Over the past few years, the FDA has approved a checkpoint blockade inhibitor called pembrolizumab, which activates T cells by blocking a protein called PD-1, to treat several types of tumors that have a high TMB.

However, subsequent studies of patients who received this drug found that more than half of them did not respond well or only showed short-lived responses, even though their tumors had a high mutational burden. The MIT team set out to explore why some patients respond better than others, by designing mouse models that closely mimic the progression of tumors with high TMB.

These mouse models carry mutations in genes that drive cancer development in the colon and lung, as well as a mutation that shuts down the DNA mismatch repair system in these tumors as they begin to develop. This causes the tumors to generate many additional mutations. When the researchers treated these mice with checkpoint blockade inhibitors, they were surprised to find that none of them responded well to the treatment.

“We verified that we were very efficiently inactivating the DNA repair pathway, resulting in lots of mutations. The tumors looked just like they look in human cancers, but they were not more infiltrated by T cells, and they were not responding to immunotherapy,” Westcott says.

The researchers discovered that this lack of response appears to be the result of a phenomenon known as intratumoral heterogeneity. This means that, while the tumors have many mutations, each cell in the tumor tends to have different mutations than most of the other cells. As a result, each individual cancer mutation is “subclonal,” meaning that it is expressed in a minority of cells. (A “clonal” mutation is one that is expressed in all of the cells.)

In further experiments, the researchers explored what happened as they changed the heterogeneity of lung tumors in mice. They found that in tumors with clonal mutations, checkpoint blockade inhibitors were very effective. However, as they increased the heterogeneity by mixing tumor cells with different mutations, they found that the treatment became less effective.

“That shows us that intratumoral heterogeneity is actually confounding the immune response, and you really only get the strong immune checkpoint blockade responses when you have a clonal tumor,” Westcott says.

Failure to activate

It appears that this weak T cell response occurs because the T cells simply don’t see enough of any particular cancerous protein, or antigen, to become activated, the researchers say. When the researchers implanted mice with tumors that contained subclonal levels of proteins that normally induce a strong immune response, the T cells failed to become powerful enough to attack the tumor.

“You can have these potently immunogenic tumor cells that otherwise should lead to a profound T cell response, but at this low clonal fraction, they completely go stealth, and the immune system fails to recognize them,” Westcott says. “There’s not enough of the antigen that the T cells recognize, so they’re insufficiently primed and don’t acquire the ability to kill tumor cells.”

To see if these findings might extend to human patients, the researchers analyzed data from two small clinical trials of people who had been treated with checkpoint blockade inhibitors for either colorectal or stomach cancer. After analyzing the sequences of the patients’ tumors, they found that patients’ whose tumors were more homogeneous responded better to the treatment.

“Our understanding of cancer is improving all the time, and this translates into better patient outcomes,” Cortes-Ciriano says. “Survival rates following a cancer diagnosis have significantly improved in the past 20 years, thanks to advanced research and clinical studies. We know that each patient’s cancer is different and will require a tailored approach. Personalized medicine must take into account new research that is helping us understand why cancer treatments work for some patients but not all.”

The findings also suggest that treating patients with drugs that block the DNA mismatch repair pathway, in hopes of generating more mutations that T cells could target, may not help and could be harmful, the researchers say. One such drug is now in clinical trials.

“If you try to mutate an existing cancer, where you already have many cancer cells at the primary site and others that may have disseminated throughout the body, you’re going to create a super heterogeneous collection of cancer genomes. And what we showed is that with this high intratumoral heterogeneity, the T cell response is confused and there is absolutely no response to immune checkpoint therapy,” Westcott says.

More information:
Peter M. K. Westcott et al, Mismatch repair deficiency is not sufficient to elicit tumor immunogenicity, Nature Genetics (2023). DOI: 10.1038/s41588-023-01499-4

This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.

Citation:
Study explains why certain immunotherapies don’t always work as predicted (2023, September 17)
retrieved 18 September 2023
from https://phys.org/news/2023-09-immunotherapies-dont.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

>>> Read full article>>>
Copyright for syndicated content belongs to the linked Source : Phys.org – https://phys.org/news/2023-09-immunotherapies-dont.html

Tags: explainssciencestudy
Previous Post

NASA joins the still controversial search for UFOs

Next Post

Texas Attorney General Paxton acquitted in impeachment trial

EIFO invests $5 million in D3, the Ukraine-focused defence technology venture fund – sUAS News

EIFO Commits $5 Million to Boost Ukraine-Focused Defense Tech Fund D3

July 6, 2025
Winning sports’ woke war is great, but unfortunately it’s led by the absurd – New York Post

Winning the Sports Culture War Is Exciting, but It’s Driven by the Absurd

July 6, 2025
Tradition, ecology, and communion: the Church experiences a week of renewal and global commitment – exaudi.org

Tradition, Ecology, and Communion: The Church’s Inspiring Week of Renewal and Global Commitment

July 5, 2025
Shriners Children’s to Establish Research Institute at Science Square – Georgia Tech News Center

Shriners Children’s to Establish Research Institute at Science Square – Georgia Tech News Center

July 5, 2025
Scientists warn US will lose a generation of talent because of Trump cuts | Trump administration – The Guardian

Scientists Warn Trump-Era Cuts Threaten to Drain a Generation of American Talent

July 5, 2025
7 outdated boomer behaviors that were once normal but now feel tone-deaf – VegOut

7 Outdated Boomer Behaviors That Once Seemed Normal but Now Feel Completely Tone-Deaf

July 5, 2025
The Conversation: Freedom in the modern world – standard.net

Embracing Freedom in the Modern World: Challenges and Opportunities

July 5, 2025
The U.S. added 147,000 jobs in June, relieving some concerns of a workforce slowdown – NBC News

U.S. Adds 147,000 Jobs in June, Easing Fears of Workforce Slowdown

July 5, 2025
Magicians and Battlebots light up Las Vegas entertainment scene – KSNV

Magicians and Battlebots Take Las Vegas Entertainment by Storm

July 5, 2025
Final House Vote on Devastating Health and Food Assistance Cuts – Medicare Rights Center

House Prepares to Vote on Major Cuts Jeopardizing Health and Food Assistance Programs

July 5, 2025

Categories

Archives

July 2025
MTWTFSS
 123456
78910111213
14151617181920
21222324252627
28293031 
« Jun    
Earth-News.info

The Earth News is an independent English-language daily published Website from all around the World News

Browse by Category

  • Business (20,132)
  • Ecology (706)
  • Economy (732)
  • Entertainment (21,621)
  • General (15,731)
  • Health (9,769)
  • Lifestyle (736)
  • News (22,149)
  • People (732)
  • Politics (740)
  • Science (15,949)
  • Sports (21,231)
  • Technology (15,716)
  • World (712)

Recent News

EIFO invests $5 million in D3, the Ukraine-focused defence technology venture fund – sUAS News

EIFO Commits $5 Million to Boost Ukraine-Focused Defense Tech Fund D3

July 6, 2025
Winning sports’ woke war is great, but unfortunately it’s led by the absurd – New York Post

Winning the Sports Culture War Is Exciting, but It’s Driven by the Absurd

July 6, 2025
  • About
  • Advertise
  • Privacy & Policy
  • Contact

© 2023 earth-news.info

No Result
View All Result

© 2023 earth-news.info

No Result
View All Result

© 2023 earth-news.info

Go to mobile version