Peripheral circulating proteomic profiling reveals serum CD80 is positively correlated with the efficacy of neoadjuvant PD-1 blockade combined with chemotherapy for esophagus cancer

Neoadjuvant immunotherapy combined with chemotherapy has achieved remarkable success in esophagus cancer. However, identifying the patients who may benefit from the neoadjuvant treatment remains a great challenge. The aim of this study was to investigate peripheral blood biomarkers and explore their underlying mechanism. Baseline blood samples were collected and analyzed from esophagus cancer patients (discovery cohort n = 46, validation cohort n = 28) treated with neoadjuvant PD-1 blockade combined with chemotherapy. To explore the underlying mechanism of the identified biomarker, pre- and post-treatment transcriptome sequencing and PD-L1 immunohistochemistry data were analyzed. A total of 55 features, including complete blood count and serum proteins were quantified from blood samples. In the discovery cohort, CD80-high patients were found to be associated with a higher response rate (AUC = 0.686). The predictive value of serum CD80 in evaluating treatment efficacy was further confirmed in the validation cohort (AUC = 0.778). Moreover, we found that patients with CD80-high were associated with higher CD8 T cells and lower neutrophils in the tumor microenvironment. During neoadjuvant treatment, iTreg infiltration and PD-L1 expression levels were significantly increased, while the MHC class I signature score was significantly decreased in patients with CD80-low. Peripheral blood circulating soluble CD80 protein may serve as a potential non-invasive biomarker to predict clinical benefit for esophagus cancer patients treated with neoadjuvant PD-1 blockade combined with chemotherapy.