Macrophages are cells of the immune system that protect the host from invading pathogens. But in cancer, macrophages can be “hijacked” by tumors, and made to support their malignant growth and spread. This is a drawback for a major cancer treatment, immunotherapy, which turns the body’s immune system against the tumor. EPFL scientists, working with colleagues at the Roche Innovation Centers in Munich and Basel, have now identified a molecular “switch” that can convert the “hijacked” macrophages into cells that can stimulate the immune system to fight the growth and spread of cancer. The work is published in Nature Cell Biology.
Along with attacking foreign pathogens like bacteria, macrophages also help the body’s organs develop and its wounds heal. Their own behavior is fine-tuned by small molecules that they produce, called microRNAs.
When a tumor begins to develop, macrophages attempt to block its growth. But often tumors hijack them and convert them into what are known as “tumor-associated macrophages”, or TAMs for short.
Now corrupted, TAMs use their microRNAs to shield the tumor from the patient’s immune system, helping it grow and metastasize. This phenomenon is common across many tumor types. It is one of the major obstacles in treating cancer, and often leads to a poor prognosis for the patient.
Michele De Palma’s team at EPFL found how to reclaim TAMs. The researchers genetically modified TAMs to remove their ability to produce microRNAs. As a result, the TAMs were reprogrammed dramatically. Instead of protecting the tumor, the TAMs now signaled the presence of the tumor to the immune system, triggering attacks against it – and did so very efficiently.
Using a bioinformatics approach, the researchers found that the most likely culprit was a small family of microRNAs, called Let-7. This offers a more specific target: blocking Let-7 microRNAs may help instruct the TAMs to stimulate anti-tumor immunity.
Interestingly, the researchers observed that reprogramming TAMs also stops cancer cells from leaving the primary tumor. This could mean that the approach can also prevent tumor metastasis, the most threatening aspect of cancer. Moreover, the researchers found that the re-educated TAMs could enhance the anti-tumoral efficacy of certain cancer immunotherapies, some of which are already approved for patients.
However, more work is needed to translate all these findings to actual therapies, especially since there is currently no way to block the Let-7 microRNAs selectively in TAMs. But De Palma’s lab is now working with bioengineers at EPFL to design drugs that can target the Let-7 microRNAs specifically in the TAMs.
Some of the most promising cancer treatments are immunotherapies, which are based on provoking or enhancing the patient’s immune response against their tumor. “The most exciting finding was that TAM reprogramming greatly improved the efficacy of immunotherapy,” says Michele De Palma. “Our results in experimental models of cancer suggest a new therapeutic strategy based on inhibiting the microRNA machinery – or the Let-7 microRNAs – specifically in the TAMs, which may unleash the power of mainstream immunotherapies, such as immune checkpoint inhibitors”.
Learn more: Reclaiming the immune system’s assault on tumors
The Latest on: Immunotherapy
via Google News
The Latest on: Immunotherapy
- What Does Real-World Data Show for Adjuvant Immunotherapy in Melanoma?on June 26, 2020 at 12:16 pm
Having lower socioeconomic status, comorbidities, or being covered by Medicare was associated with less receipt of immunotherapy for stage III melanoma.
- Global Immunotherapy Drugs Market 2020 Industry Emerging Trend, Market Players, Revenue Insights to 2026on June 26, 2020 at 5:46 am
The report provides rational insights along with historical and forecast data to aid in better understanding of ...
- ERC Belgium Submits Marketing Authorization Application to European Medicines Agency (EMA) for Glioblastoma Immunotherapy, SITOIGANAPon June 25, 2020 at 9:00 pm
ISNES, Belgium--(BUSINESS WIRE)--ERC Belgium, a clinical-stage biopharmaceutical company developing immunotherapies for the treatment of cancer, has announced that it has submitted to the EMA its ...
- Cancer Immunotherapy Tied to Severe COVID-19 Outcomeson June 25, 2020 at 1:22 pm
Cancer patients receiving immunotherapy were at increased risk for severe outcomes from COVID-19, according to retrospective findings from Memorial Sloan Kettering Cancer Center in New York City.
- Immunotherapy shows potential in treating lung fibrosison June 24, 2020 at 9:18 am
New research suggests that lung fibrosis develops when scar tissue cells escape immune surveillance, suggesting potential therapy.
- Research uncovers clues in use of immunotherapy for breast canceron June 24, 2020 at 9:01 am
UC researchers have found a potential new combination therapy for breast cancer that would integrate use of the body's immune system with targeted treatment for a particular protein that advances ...
- Engineering a better immunotherapy to outwit cancer — and launch a biotechon June 24, 2020 at 8:07 am
Tweaking an immune protein called interleukin-18 can overcome tumors that lure it into binding with a decoy receptor protein, new research in mice shows.
- Immunotherapy for breast canceron June 24, 2020 at 7:05 am
UC researchers have found a potential new combination therapy for breast cancer, involving use of the immune system.
- Real-World Data Back Immunotherapy in Stage III Melanomaon June 22, 2020 at 3:17 pm
Treatment with adjuvant immunotherapy conferred a survival advantage for patients with resectable melanoma at the highest risk of relapse, real-world evidence from the National Cancer Database (NCDB) ...
- Study shows new way of identifying tumor response to immunotherapyon June 22, 2020 at 12:01 pm
Scientists at City of Hope, working in collaboration with researchers at Translational Genomics Research Institute (TGen) and other colleagues across the country, have found that the actions of ...
via Bing News