Monitoring the immune response before, during, and after treatment
Neo-antigen production by tumor cells
An antigen is a substance that is generally foreign to the body and may trigger an immune response by causing the formation of antibodies by lymphocytes.
Mutations within the tumor genome can induce the expression of tumor-specific mutant proteins which aren’t expressed by normal cells. These proteins are recognized as foreign and constitute what we call neo-antigens.
Some neo-antigens provoke an immune response but it’s usually too weak to eradicate the tumor. The ability to identify these neo-antigens, understand the associated immune reaction and activate the immune system to make it more efficient is a major challenge for oncologists. Knowing that these neo-antigens are expressed exclusively on tumor cells they are a preferred therapeutic target as the risk of provoking an auto-immune reaction should be minimal.
Recognition of neo-antigens by T-cells
T cells are major players in immune response. They have an extraordinary capacity to recognize antigens in their diverse forms. This is possible as each T cell clone has a unique receptor (TCR: T cell receptor) allowing it to recognize a single antigen (or neo-antigen). All of the clones make up the T cell repertoire.
Link between the T cell repertoire and the therapeutic response
Recent studies show a link between the T cell repertoire and the therapeutic response. Increased frequency of T cells expressing recurrent T cell repertoires during treatment (immune checkpoint inhibitor or conventional treatment) would reflect an anti-tumor immune response during treatment.
New biomarkers to guide therapeutic choices
Eliane Piaggio, Olivier Lantz
Monitoring the evolution of T cell repertoires in patients during treatment, whether by immune checkpoint inhibitors or other treatments, could enable us to evaluate the response to treatment. To verify this hypothesis we will use an innovative high throughput single cell analysis technique. In the case of patients who react favorably it may be interesting to look for the neo-antigens responsible for the anti-tumor reaction.