Lymphocyte activation markers predict the therapeutic response to immune checkpoint inhibitors: A case–control study

Abstract Background Reports on changes in circulating immune cells induced by immune checkpoint inhibitors (ICIs) and their association with therapeutic responses are limited. This study aimed to analyze the interaction between ICIs and circulating blood cells in real‐world practice and identify biomarkers associated with therapeutic efficacy. Materials and Methods Patients with non‐small cell lung cancer who received nivolumab, pembrolizumab, or atezolizumab monotherapy were eligible. Blood samples were collected before and 7–21, and 22–42 days after treatment, and changes in the number and characteristics of neutrophils and lymphocytes in the peripheral blood were analyzed. The efficacy of ICIs was evaluated based on the best overall response up to 3 months after treatment. The patients were divided into the following groups: patients with non‐progressive disease (non‐PD) and those with progressive disease (PD). Blood immunological factors related to treatment response were analyzed. Results There were 16 and 27 patients in the non‐PD and PD groups, respectively. The non‐PD group had significantly lower pretreatment CD56 + cell (CD56 + IFN‐γ + cell), and neutrophil counts at 7–21 days after ICI administration than the PD group. Additionally, there was a significant increase in CD8 + IFN‐γ + , and CD8 + CD28 + IFN‐γ + T‐cell counts 7–21 days after ICI administration in the non‐PD group. CD8 + CD28 + IFN‐γ + T‐cell count greater than 94.6 cells/μL at 7–21 days after ICI administration was highly predictive with an AUC greater than 0.8 in the ROC curve analysis. Conclusions Predictors of disease progression include a low activated CD56 + cell count, no increase in the neutrophil count before ICI therapy, and an increase of activated CD8 + cell count early after ICI administration. The findings will contribute to selecting patients with a favorable therapeutic response and early prediction of therapeutic response to ICI.