The effect of immune cell traits on efficacy and adverse drug reactions of platinum drugs： A Mendelian randomization analysis

Background: Platinum drugs are widely used in tumor chemotherapy, but the immune characteristics of different individuals have different effects on the sensitivity and side effects of platinum drugs. Therefore, we use Mendel randomized analysis to study whether peripheral blood immune cells have a causal relationship with the efficacy and adverse reactions of platinum drugs. Methods We used 731 kinds of peripheral blood immune cell traits of 3757 healthy individuals and 429 patients with non-small cell lung cancer (NSCLC) in Xiangya Hospital of Central South University to conduct a Mendel randomized analysis with two samples, in order to find out the causal relationship between some immune cell traits and the efficacy and adverse reactions of platinum drugs. Results First of all, we found 28 immune cell traits significantly related to the efficacy of platinum drugs, including 16 protective factors and 12 risk factors. Secondly, the protective factors of renal injury, BAFF-R is our focus, accounting for one third of all factors. Finally, we found that naïve-mature B cell is a protective factor for gastrointestinal upset and cutaneous toxicity. Conclusions This study emphasizes that B cell-related traits mainly affected gastrointestinal upset and cutaneous toxicity, while T cell-related traits mainly affected other outcome variables. These findings may promote our understanding of the relationship between the efficacy and adverse reactions of platinum drugs and the immune system, and promote the future development of biomarkers for predicting the efficacy and adverse reactions of platinum drugs.