Causal effects of immune cells on the efficacy and adverse drug reactions of platinum drugs

Platinum drugs are widely used in lung cancer chemotherapy, but the immune characteristics of different individuals have different effects on the sensitivity and side effects of platinum drugs. In this study, we use 731 kinds of 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 in order to find out the causal relationship between some immune cell traits and the efficacy and adverse reactions of platinum drugs. We find that CD19 on CD24 ⁺CD27 ⁺ B cell (OR = 0.598, <i>P</i> = 0.004) is the most significant immune cell trait as the protective factor of efficacy. HLA-DR ⁺CD8 ⁺ T cell % lymphocyte (OR = 0.427, <i>P</i> = 7.55 × 10 ^-4) and HLA-DR ⁺CD8 ⁺ T cell % T cell (OR = 0.471, <i>P</i> = 0.003) are the protective factors of liver injury. CD39 on CD39 ⁺ secreting CD4 ⁺ regulatory T cell (OR = 28.729, <i>P</i> = 0.009) and CD3 on CD39 ⁺ resting CD4 regulatory T cell (OR = 3.024, <i>P</i> = 0.009) are the risk factors of renal injury. Meanwhile, B cell-related traits mainly affect gastrointestinal upset and cutaneous toxicity, while T cell-related traits mainly affect 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 future development of biomarkers for predicting the efficacy and adverse reactions of platinum drugs.