Biomarqueurs prédictifs de réponse aux inhibiteurs de points de contrôle immuns

Abstract

PREDICTIVE BIOMARKERS OF RESPONSE TO IMMUNE CHECKPOINT INHIBITORS: PD-1 checkpoint inhibitors are becoming the reference treatment for several types of cancers. Many patients show remarkable efficacy and low toxicity. However, some patients have a better outcome than others with PD-1 checkpoint inhibitors. So, it is crucial to identify biomarkers of response. We review here the available data of several potential biomarkers of efficacy. The expression of PD-L1, detected by immunohistochemistry on tumor cells and immune cells is a good predictive biomarker of response for some cancers; however, this method is not standardized, and there are different antibodies, different cut-off values, and different targets (tumor or microenvironment). Moreover, the expression of PD-L1 is dynamic and heterogeneous within the tumor: expression is discordant between primary tumor and metastasis or between biopsy and surgical specimen. Peripheral blood lymphocytes also can be informative, especially the baseline neutrophil to lymphocyte ratio which is easy to measure in daily practice. High rate of neoantigens is also associated with improved response. Therefore, mutation burden can be predictive of response and this explains why tumors with microsatellites instability have an enhanced response. Similarly, genetic signatures are linked with resistance or response to treatment. Gut microbiota is associated with improved antitumor immune response although the underlying mechanism is not well understood so far. Lastly, it seems that cytokines, mediators of immunity may play a role in the response to immunotherapy and so, constitute an interesting biomarker. Several potential biomarkers are identified but none is prospectively validated so far.

Keywords: Anti-PD1; Biomarkers; Biomarqueurs; Expression de PD-L1; Immunotherapy; Immunothérapie; PD-1 blockades; PD-L1 expression.