Colorectal Cancer’s Immunotherapy Shield Broken: โฃNew Targetsโข Emerge
Table of Contents
- Colorectal Cancer’s Immunotherapy Shield Broken: โฃNew Targetsโข Emerge
- TGF-ฮฒ: Theโข “Noโฃ Entry” Signal for Immuneโ Cells
- The Path forward: Expanding Immunotherapy’s Reach
- Evergreen Context: Immunotherapy and Colorectal cancer
- Frequently Asked Questions
- What is โTGF-ฮฒ and why is it important in cancer?
- How does โthis research improve our understanding of immunotherapy resistance?
- What are the next steps in translating this research into clinical practice?
- Areโค there any current treatments that target TGF-ฮฒ?
- What is the tumor microenvironment?
Barcelona, Spain – November 8, 2025 07:16:30 โCET – A groundbreakingโ study has unveiled a key mechanism by which metastatic colorectal cancer resists immunotherapy, โpaving the way for the development of moreโค effective treatments.Researchers have discovered that the protein TGF-ฮฒโ effectively hides tumors from the immuneโ system, โand identified potential strategies to overcome this defense. โThis finding is particularly significant as immunotherapy currently benefits only a limited subset of patients with this aggressive disease.
Colorectal cancer is the third most common cancer diagnosed in both men and โฃwomen in the United States, โฃwith an estimated 153,020 new cases expected โคin โ2024, โฃaccordingโ to the American Cancer Society 1. Immunotherapy, which harnesses the body’s own โคimmune system to โฃfight cancer, has shown promise in treating various cancers, but its effectiveness in colorectal cancer โhas been โlimited. This newโค research explains why, and offers a roadmap for improving outcomes.
TGF-ฮฒ: Theโข “Noโฃ Entry” Signal for Immuneโ Cells
The research, a collaboration between the Institute for Research in Biomedicine (IRB Barcelona) and the National Center for Genomic Analysis (CNAG), utilized advanced single-cell sequencing technology toโ analyze theโ tumor microenvironment.By sequencing individual โcells within theโ tumour microenvironment, we have been able โฃto characterise theโข main players affected by TGF-ฮฒ,
explains Dr. Holger Heyn,โ Single Cellโ genomics โขGroup Leader at CNAG and ICREA Research Professor. The team found that TGF-ฮฒ prevents T cells, the immune โฃsystem’s primary cancer fighters, from reaching the tumor.
Simultaneously, TGF-ฮฒ alters macrophages, a type of immune cell, โcausing them to produceโข a proteinโ called osteopontin. This protein further suppresses theโ activity of any T cells that do manage to infiltrate the tumor,effectively rendering the cancer invisible โto the immuneโ system. In our experimental models, when weโฃ block the action of TGF-ฮฒ, the immune cells were able to massively โenter the tumour and regain their capacity โขto attack,
โ stated Dr. Ana Henriques, the paper’s first author.
Blocking TGF-ฮฒ: A Potential Breakthrough
When researchers blocked TGF-ฮฒ in experimental models, they observed a significantโฃ influx ofโข immune cells into the tumor and a restoration of their ability to attack cancerโ cells. Furthermore, combining TGF-ฮฒ blockadeโ with existing immunotherapy resulted in very potent anti-tumour responses,
according to co-author โDr. Mariaโ Salvany.
| Mechanism | Effect |
|---|---|
| TGF-ฮฒ | Blocks T cell circulation |
| TGF-ฮฒ & Macrophages | Increased Osteopontin production |
| Osteopontin | Suppresses T cellโค multiplication |
| TGF-ฮฒ โBlockade | Enhanced immune โคcell infiltration |
Did You Know?
Colorectal cancer is frequently enough preventable through โregular screening, such โas colonoscopies,โ whichโ can detect and remove precancerous polyps.
While clinical trials for TGF-ฮฒ inhibitors already exist, their use isโค currently limited by significant side effects.โค This study suggests that targeting โฃthe mechanisms activated *by* TGF-ฮฒ – such as osteopontin production โข- could offer a safer and more selective approach.In any case, these alternatives will need to โฃbe evaluated in clinical trials, and always in combination with immunotherapy,
commented Dr. Eduard Batlle.
Pro Tip:
Staying informed about โthe latest cancer research and discussing treatment options with your healthcare provider is crucial for making informed decisions โabout your health.
The Path forward: Expanding Immunotherapy’s Reach
Understanding this circuit allows us โto search for safer and moreโค selective solutions. โThe ultimate goal for immunotherapies, which today only work in a small group of patients, to be able to also benefit the majority of those with metastatic colorectal cancer,
concludes Dr.โ prados, now a researcher at the โUniversity of Granada. The research team hopes their findings will accelerate โคthe development of new therapies that can overcome immunotherapy resistance andโค improve outcomes for patients with thisโ challenging disease.
The study was funded by the Olgaโข Torresโค Foundation, “la Caixa” Foundation, World Wide Cancer Research, the โขEuropean Research Council (ERC Advanced Grant), the Spanish Association โขagainst Cancer (AECC)โ through the โExcellence Program and other grants for researchers, the Ministry of Science, Innovation and Universities, La Maratรยณ de TV3, and the Agencyโค for Management of University โคand Research grants (AGAUR).
What are your thoughts โฃon the potential of targeting TGF-ฮฒ in colorectal cancer treatment? Shareโ your viewpointโ in the comments below!
If you foundโ this article informative, โplease share it โขwithโ your networkโ to help raise awareness about this crucial research.
Evergreen Context: Immunotherapy and Colorectal cancer
Immunotherapy has revolutionized cancer treatment in recent years, but its success varies significantly depending on the type of cancer. While highly effective in cancers like melanoma and lung cancer, colorectal cancer has provenโฃ moreโ resistant. this resistance is often attributed to the tumor microenvironment,which can suppress the immune system. The โtumor microenvironment โขis a complex ecosystem surrounding the tumor, consisting of immune cells, blood vessels, and โคother supporting โcells. Understanding how this habitat influences immunotherapy response โis a major focusโ of current cancer research.
Frequently Asked Questions
What is โTGF-ฮฒ and why is it important in cancer?
TGF-ฮฒ is a protein thatโ plays a complex role in cancer. While it can initially suppress tumor growth,it often contributes to cancer progressionโฃ by suppressing the immune system and promoting โmetastasis.
How does โthis research improve our understanding of immunotherapy resistance?
This research identifies a specific mechanism – TGF-ฮฒ-mediated immune suppression – that contributes to immunotherapy resistance โin colorectal cancer, providing a potentialโข target for new therapies.
What are the next steps in translating this research into clinical practice?
Theโ next steps involve evaluating โฃalternative strategies toโฃ block TGF-ฮฒ signaling, โsuch as targeting osteopontin production, in clinical trials, always in combination with immunotherapy.
Areโค there any current treatments that target TGF-ฮฒ?
Yes, clinical trials are ongoing for TGF-ฮฒ โinhibitors,โ but their use isโ currently limited by side effects. This researchโฃ aims to identify safer and more โฃselective approaches.
What is the tumor microenvironment?
The tumor microenvironment is the complex โฃecosystem surrounding a tumor, includingโข immune cells, blood vessels, and other supporting cells.โข It playsโข a crucial role in cancer progression and responseโ to treatment.