Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breaking through a tumor's defenses

08.06.2018

Understanding how tumors subvert elements of our immune system suggests new immunotherapy treatments

  • Researchers identify the dominant immune cells contributing to tumour tolerance by the immune system
  • Silencing the tumour-shielding cells of the immune system allows T cell attack on tumours and restricts tumour growth
  • Research findings suggest new targets for cancer immunotherapies

View of cells within a mouse tumor with increasing magnification. TAMs show red fluorescence and anti-tumor T cells show magenta fluorescence.

Image credit: Dr Fabien Garcon, Babraham Institute

In research published today, Babraham Institute researchers have shown that some tumours use not one but two levels of protection against the immune system. Knocking out one level boosted the protective effects of the second and vice versa. The research demonstrates that a two-pronged approach targeting both cell types simultaneously may offer a promising route for the development of new cancer immunotherapies.

The development and growth of a cancerous tumour often occurs despite a fully functioning immune system, capable of recognising and killing cancer cells. Tumours hijack certain cells in our immune system to create a growth-permissive environment and give protection from the anti-tumour elements. In particular, tumours recruit immune cell allies, cells called tumour-associated macrophages (TAMs) and regulatory T cells (Treg), to evade immune attack.

Specifically inhibiting the recruitment of TAMs by blocking the actions of a protein called colony-stimulating factor 1 (CSF1) reduces tumour growth in mouse models. Although clinical trials of inhibitors targeting TAMs are underway, results in patients haven't been as effective as hoped. A lack of understanding of how TAMs promote tumour progression potentially limits the therapeutic value of these inhibitors.

Likewise, inhibiting the action of Treg cells in mice by inactivating a key enzyme called PI3K delta gives protection against a range of tumours. A PI3K delta inhibitor is approved for treatment of chronic lymphocytic leukaemia (CLL) and follicular non-Hodgkin lymphoma (NHL), but the potential for PI3K delta inhibitors for the treatment of solid cancers in humans is yet to be demonstrated.

The research published today used a mouse model of colorectal cancer to explore the synergy between TAMs and Treg cells, showing that each cell type was able to compensate for the effects of the loss of the other to maintain the tumour's protection from the immune system. However, jointly inhibiting TAMs and Treg cells substantially inhibited tumour growth.

Dr David Gyori, first author on the paper, said: "Strikingly, preventing tumour immunosuppression by both TAMs and Treg cells caused almost complete tumour rejection by the immune system and half of the mice became completely tumour-free. Taken together, our findings provide a convincing rationale for assessing the clinical value of combinatorial therapies targeting the CSF1 receptor and PI3K delta."

Professor Klaus Okkenhaug, one of the authors on the study by Gyori et al. and a parallel study by Lim et al. said: "Harnessing the power of the immune system to kill cancer cells is becoming a successful therapeutic strategy. These studies demonstrate the importance of fully understanding the interplay between the many elements of the immune system to ensure that combinatorial therapies are both synergistic and effective."

Louisa Wood | EurekAlert!
Further information:
https://www.babraham.ac.uk/news/2018/06/breaking-through-a-tumours-defences
http://dx.doi.org/10.1172/jci.insight.120631

Further reports about: PI3K TAMs cancer cells immune system immunotherapies key enzyme tumour tumour growth

More articles from Life Sciences:

nachricht Exciting Plant Vacuoles
14.06.2019 | Julius-Maximilians-Universität Würzburg

nachricht A microscopic topographic map of cellular function
13.06.2019 | University of Missouri-Columbia

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

Im Focus: Tube anemone has the largest animal mitochondrial genome ever sequenced

Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.

The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....

Im Focus: Tiny light box opens new doors into the nanoworld

Researchers at Chalmers University of Technology, Sweden, have discovered a completely new way of capturing, amplifying and linking light to matter at the nanolevel. Using a tiny box, built from stacked atomically thin material, they have succeeded in creating a type of feedback loop in which light and matter become one. The discovery, which was recently published in Nature Nanotechnology, opens up new possibilities in the world of nanophotonics.

Photonics is concerned with various means of using light. Fibre-optic communication is an example of photonics, as is the technology behind photodetectors and...

Im Focus: Cost-effective and individualized advanced electronic packaging in small batches now available

Fraunhofer IZM is joining the EUROPRACTICE IC Service platform. Together, the partners are making fan-out wafer level packaging (FOWLP) for electronic devices available and affordable even in small batches – and thus of interest to research institutes, universities, and SMEs. Costs can be significantly reduced by up to ten customers implementing individual fan-out wafer level packaging for their ICs or other components on a multi-project wafer. The target group includes any organization that does not produce in large quantities, but requires prototypes.

Research always means trying things out and daring to do new things. Research institutes, universities, and SMEs do not produce in large batches, but rather...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Concert of magnetic moments

14.06.2019 | Information Technology

Materials informatics reveals new class of super-hard alloys

14.06.2019 | Materials Sciences

New imaging modality targets cholesterol in arterial plaque

14.06.2019 | Medical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>