Early detection and treatment of cancer is critical for patients suffering from the disease. Researchers led by Jérôme Galon and Céline Mascaux at the Centre de Recherche des Cordeliers (Inserm/Université de Paris/Sorbonne Université) have now discovered that the body’s immune response is activated as soon as precancerous cells appear in the very first stages of lung cancer. The result, which is reported in Nature, suggests that immunotherapy early on could help prevent a cancer from progressing.
Current cancer treatments involve surveying precancerous lesions in lung cancer and removing these if there is the slightest suspicion that they could lead to cancer. The new results from Jérôme Galon’s team imply that it could be possible, at this early stage, to target the immune system itself to prevent these lesions from getting worse.
The researchers analysed 122 lung biopsies from smokers at risk of lung cancer. They found evidence of all the stages of pre-cancerous to cancerous lesions in the samples.
They employed gene-expression profiling and multispectral fluorescence, an imaging technique based on the use of specific antibodies targeting different types of immune cells. This approach allowed them to characterize the nature, quantity and disposition of the different immune actors in the tumour micro-environment at each pre-cancerous and cancerous stage.
The team identified how the trajectories of cancer evolved and the immune response involved. At the low-grade, extremely early, dysplasia stage, in which cells simply show some morphological abnormalities, DNA repair defects and a greater ability to divide, they observed the activation of local immune cells and the arrival of naïve (that is, uneducated) T cells to specifically destroy the abnormal cells. At the high-grade dysplasia stage, which corresponds to more important morphological and molecular cell abnormalities, they saw a massive recruitment of innate and adaptive immunity with the presence of B and T lymphocytes specific for abnormal cells and the deployment of the memory immune response.
The problem is that this deployment is already accompanied at this stage by the appearance of immune system blocking points (known as checkpoints) and suppressive cytokines (molecules that also block the immune response). This means that immune system function is impaired even before the cancer itself manifests.
The researchers say they would now like to confirm their result in other types of cancer such as colon cancer.
They believe that carcinogenesis in the lung involves the dynamic co-evolution of pre-invasive bronchial cells and the immune response and stress the importance of discovering immune biomarkers to better predict the risk of pre-cancerous lesions progressing to cancer.
Jérôme Galon was recently awarded the 2019 European Inventor Award in the “Research” category of the European Patent Office for the development of Immunoscore, an immunological test that predicts the risk of recurrence in cancer patients.
Read the research paper: Immune evasion before tumour invasion in early lung squamous carcinogenesis, Céline Mascaux et al. Nature 10.1038/s41586-019-1330-0