Immune biomarkers in circulating cells of NSCLC patients can effectively evaluate the efficacy of chemotherapy combined with anti-PD-1 therapy

Jing Cao ¹ Yuehua Zhang ² Shenghu Guo ² Zheng Wu ² Xiaojin Guo ² Rongze Zhang ² Lei Zhang ² Ya Liu ² Xing Li ² Chunwang Yang ² Dongwei He ² Lu Bai ² Tingting Lv ² Yong Xie ³ Chengjing Huang ⁴ Shuang Xiao ⁵ Anyi Deng ⁵ Jiawei Li ^4,5 Jiaxing Zhu ⁶ Zhenghu Jia ^5,6* Zhinan Yin ^5* Zhiyu Wang ^2*

• ¹ Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
• ² Department of Immune-Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
• ³ Department of Obstetrics and Gynecology, First People's Hospital of Foshan, Foshan, Guangdong Province, China
• ⁴ Jiangxi Purui Biotechnology Co., Ltd., Ganzhou, China
• ⁵ Biomedical Translational Research Institute, Jinan University, Guangzhou, China
• ⁶ Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China

The application of programmed cell death protein 1 (PD-1) antibodies has brought significant benefits to patients with non-small cell lung cancer (NSCLC). However, not all patients respond to PD-1 immune therapy. The aim of this study was to identify response biomarkers to predict the efficacy of chemotherapy combined with anti-PD-1 therapy in NSCLC patients. Thirty-two NSCLC patients receiving chemotherapy combined with anti-PD-1 therapy were recruited, and peripheral blood samples were collected before and after treatment. Flow cytometry was used to detect the proportions of circulating T-cell subsets, and cytokines in the blood serum were detected via ELISA. The results revealed that, among the CR/PR group (CR, complete response; PR, partial response; n = 22), the proportions of CD3+TIM-3+PD-1+, CD3+CD4+TIM-3+PD-1+, and CD3+CD8+TIM-3+PD-1+, CD3+γδT+PD-1+, CD3+γδT+Vδ1+PD-1+, and CD3+γδT+Vδ2+PD-1+T cells were lower after treatment, with no significant differences found between the stable disease (SD) and progressive disease (PD) groups (n = 10). Some proinflammatory cytokines are highly expressed in patients with NSCLC. This study suggests that monitoring changes in immune biomarkers in the circulating cells of NSCLC patients may help differentiate CR/PR patients from SD/PD patients, providing a potential new approach for assessing the efficacy of chemotherapy combined with anti-PD-1 therapy.