Spots Global Cancer Trial Database for Prospective Cohort Study of Immunotherapy Resistance in Metastatic Colorectal Cancer Patients With MSI

Study Description

Brief Summary: Over the last ten years, the discovery of the mechanisms by which tumours escape the control of the immune system, and in particular the T lymphocyte response, has led to the emergence of new therapeutic strategies against cancer, such as the use of "immune checkpoint inhibitors" (ICI). The immune system plays a crucial role in controlling tumour proliferation, and involves several players. Schematically, after recognition of the MHC-peptide complex by the TCR, the T lymphocyte response is modulated by several activating or inhibiting co-stimulatory signals (or "checkpoints"). The balance of these different signals determines whether the T lymphocyte (LT) is activated, resulting in the destruction of the target cell, or whether the T lymphocyte is inhibited (anergy), inducing immune tolerance. By hijacking this system through the expression of inhibitory checkpoints on its surface, the tumour cell is able to evade the effector immune response (1). Monoclonal antibodies (mAbs) directed against inhibitory co-stimulatory molecules such as Programmed-cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) or their ligand Programmed-cell death ligand 1 (PD-L1) have been developed to restore effective anti-tumour immunity. These ICIs have led to a major improvement in the prognosis of certain cancers, notably melanoma and non-small cell lung cancer. However, the efficacy of ICIs varies from one cancer to another. In addition to the expression of PDL1 by the tumour and/or immune cells, and the mutational load, one of the primary factors predicting response to immunotherapy mentioned in several studies is microsatellite instability (MSI).

Detailed Description: In order to meet our objectives, we plan to construct a retrospective and prospective, multicentre cohort. National recruitment will be carried out in all French centres, including the FFCD, AGEO, GERCOR, and UNICANCER, representing more than 150 centres and the majority of French sites, public and private hospitals. A total of 600 patients are expected. Some will be included retrospectively over the last two years prior to the launch of the prospective cohort. The theoretical duration of inclusion is set at 2 years. All patients will be followed up for 3 years.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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