Cancer: the superpower of the colon to fight against metastases, a major Toulouse discovery

In scientific research, sidesteps often make it possible to flush out treasures. And this is what the T2i (1) team at the Cancer Research Center in Toulouse did. By working on colon cancer, Christel Devaud noticed, from 2018, that the intestine plays a key role in the development of the tumor: by controlling its own immune system, it can cause the tumor to regress. Faced with this superpower, she decides to adopt a new approach. “We wanted to understand cancer immunity as a whole, which means also looking at metastases. Because a patient with colorectal cancer rarely dies from the primary tumor. But for that, we had to study tumors in vivo and directly in the organs”, explains Dr Christel Devaud, research fellow at the IUCT-Oncopole and the CRCT.

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Gut immunity agents act at a distance

Thanks to the microsurgery model developed by Virginie Feliu, research engineer at the IUCT-Oncopole and the CRCT, the team observes the colon tumor and its metastases in the liver of mouse models. “We implanted a tumor, from tumor cells, in the intestine and liver of our mice because that’s the only way to see the relationship between the tumor and the organs, like in humans. is much longer and more complicated to perform than in experiments usually done in laboratories where the tumor is positioned under the skin of mice. And, instead of modeling a single tumor, we have reproduced, in our mice, a colorectal cancer metastatic”, adds Virginie Feliu.

And there surprise. The researchers note that the immune system of the intestine is capable of acting remotely on the metastases present in the liver, as if a dialogue between the primary tumor of the colon and its metastases in the liver were taking place. The TCD8 lymphocytes of the intestine, more commonly called “killer lymphocytes”, thus attack the tumor and spread their warlike signal to the metastases so that they are also eliminated. The researchers were able to identify this interaction using integrin α4β7, a specific marker for killer lymphocytes present in the intestine. The journal Science Immunology, which is one of the top 10 journals dedicated to fundamental research, has just published this work by the Toulouse team.

To understand the illustration above: LTCD8 lymphocytes show a particular marker when they come from the intestine. A team from Toulouse has shown that these lymphocytes also act on metastases in the liver.

Identify patients who will respond to immunotherapies and vaccinate others

“There is a tremendous opening here for research against cancer. Since the immune system of the intestine plays a central role in the fight against tumors, it is certainly possible, thanks to a vaccination, to educate this immunity when it is lacking in the patient. We are therefore looking for a way to specifically stimulate the immunity of the intestine. This is a new and targeted approach, different from the classic vaccination which consists in circulating throughout the body the killer agents of tumours”, emphasizes Christel Devaud.

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The Toulouse discovery also opens up shorter-term perspectives in terms of the personalization of treatments. Since killer lymphocytes from the intestine circulate in the blood to attack tumors in the liver, we must be able to detect their presence by a biological analysis and therefore identify the patients who will respond best to immunotherapy treatments.

“For the first time, we are showing that intestinal immunity can play a role in overall immunity. By seeking to develop tumour-specific T cells, we are making further progress in the development of cancer vaccines in Toulouse, which is not a utopia”, concludes Prof. Maha Ayyoub, co-director of the T2i team.