The power of the intestine against metastases

Intestinal α4b7 CD8 T lymphocytes, activated locally in colon tumours, are key effectors of antitumour immunity and can exert systemic effector functions leading to the control of metastatic disease. This is demonstrated by the work of Christel Devaud, an Inserm researcher at the CRCT in Maha Ayyoub’s team, published on 8 June 2023 in Science Immunology and put into perspective in the journal Science on the same day.

Over the last decade, immunotherapy has revolutionised the management of oncology patients. Current immunotherapy strategies are based on monoclonal antibodies that remove the brakes on patients’ pre-existing anti-tumour T lymphocytes. Despite the immunogenic nature of colorectal cancer (CRC), immunotherapies, which have been proven in the majority of clinical trials in patients with metastatic colorectal cancer (mCRC), are unfortunately proving to be only marginally effective. Liver metastases, the most common form of CRC, are particularly difficult to treat.

Using an original model of mCRC in mice, in which tumours are implanted orthotopically, i.e. in the colon and in the metastatic sites, Feliu et al. discovered that colon tumours can stimulate antitumour CD8+ T lymphocytes, which are spontaneously capable of controlling the growth of the primary tumour but also of distant metastases, particularly in the liver. These effector CD8+ T lymphocytes, which play a decisive role in controlling metastases, have an intestinal origin, confirmed by the expression on their surface of integrin α4b7, which is responsible for the localisation and intestinal retention of immune cells. The results, obtained in mice, were validated by an analysis of CD8 a4b7 T lymphocytes in the metastases and blood of mCRC patients treated with immunotherapy.

The prospects for these results are twofold. From a fundamental research point of view, this work demonstrates a role for intestinal immunity in the systemic immunomonitoring of cancer and opens the way to exploring its underlying mechanisms and pathophysiological role. This could open up clinical prospects in the longer term, including the development of new immunotherapy strategies to control metastatic disease in CRC.

Find out more on the ACIR website
https://acir.org/weekly-digests/2023/june/new-checkpoint-might-be-involved-in-icb-resistance-in-colon-cancer