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Researchers have uncovered how tumors exploit tenascin-C to deflect the body’s natural defence against them.

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The interplay between cancer cells and immune cells is a key determinant of tumor survival. The immune system detects developing tumors, and mounts an efficient defence against them. However, successful tumors develop a number of effective strategies to evade elimination.

New research from the Kennedy Institute reveals how the production of tenascin-C, a matrix molecule that is absent from most healthy adult tissues, can be produced by a tumor to evade suppression by the body's natural defence.

Published today in Cancer Immunology Research, a journal of the American Association for Cancer Research, the paper: 'Matrix-targeting immunotherapy controls tumor growth and spread by switching macrophage phenotype', reveals a new approach to targeting tumor-specific macrophage polarization that may be effective in controlling the growth and spread of breast tumors.

"The function of tenascin-C made by the host is to activate inflammation that destroys the tumor. However, in this study we were surprised to find that in order to subvert host defence, tumors also produce tenascin-C," said Kim Midwood, Professor of Matrix Biology at NDORMS. "In this project we manipulated the expression of tumor-derived tenascin-C to make tumors that made either high, or low, levels of tenascin-C. In that way, we were able to observe how the tumor used its own tenascin-C to direct macrophages to change from a population designed to kill tumors, into a pathogenic population that could suppress the immune response, effectively turning off host defence."

In this pre-clinical trial, therapeutic antibodies were shown to be effective at blocking the activation of tumor-derived tenascin-C to stop growth and prevent the tumor spreading. This therapeutic potential of targeting tumor-specific macrophages, when used in combination with other T cell therapies, may be effective in improving the prognosis for patients with many solid cancers.

The first author of the study, Dr Claire Deligne, said: "Using the hosts' own immune response to specifically eliminate a growing tumor has proven to be an extremely successful therapeutic approach for cancer-bearing patients over the last few years. In this study, we used the understanding of the protumoral impact of tenascin-C on macrophages to demonstrate that neutralising this molecule with an antibody-based treatment could help control tumor growth as well as its spreading to the lungs, paving the way for a potential new immunotherapy."

The study was funded by Nascient Ltd., the Medical Research Council (MRC), and Worldwide Cancer Research. Dr Helen Rippon, Chief Executive of Worldwide Cancer Research, said: "Immunotherapy is emerging as a powerful new treatment option for people with cancer. But it doesn't work the same for every patient because cancer has a tricky way of evading the effects of immunotherapy. This exciting new finding reveals new information about the biology of cancer that will help scientists develop ways to improve the effectiveness of immunotherapy. This research highlights exactly what we strive to do at Worldwide Cancer Research – to find and fund bold new ideas in cancer research that will end the suffering caused by cancer."

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