The clinical prognostic value of CTCs has been being studied for years, but its predictive effect on immunotherapy is still insufficient. In this section, we will focus on the prognostic value of two aspects: the number and biological characteristics of CTCs (Additional file
2: Table S2). Mao et al. [
10] found a significant decrease in the number of CTCs on days 7 and 30 after natural killer (NK) cell treatment in stage IV NSCLC, which may be related to the tumor shrinking. The tumor volume shrinks after NK cell treatment, which reduces the number of CTCs released from the lesion into the blood. Therefore, CTCs could be a useful biomarker for evaluating the efficacy of NK cell therapy. In another study of NK cell immunotherapy in hepatic carcinoma [
11], a similar correlation was also observed. In addition, a study that aimed to investigate the safety and short-term efficacy of irreversible electroporation (IRE) combined with NK cell immunotherapy found that CTC number may reflect the efficacy of the combination therapy in unresectable primary liver cancer [
12]. Currently, programmed cell death ligand 1 (PD-L1) expression is the most established predictive biomarker of the response to drugs that target the PD-L1/programmed cell death protein 1 (PD-1) axis [
13‐
15]. To assess PD-L1 expression in tumors, tissue PD-L1 biopsy is a common method. However, this puts patients at risk of complications and delayed reports, and the limited sample may be inadequate to represent the overall tumor heterogeneity. PD-L1 expression on CTCs could offset the shortcoming of tissue PD-L1 biopsy. In patients treated with PD-1 inhibitor, pretreatment PD-L1+ CTCs are associated with their poor prognosis [
16]. Based on PD-L1 expression on CTCs, after patients were treated with nivolumab for 6 months, they all obtained a clinical benefit in the group with PD-L1(−) CTCs, while they all experienced progressive disease in the PD-L1(+) CTC group [
17]. In addition to NSCLC, CTCs are also predictors of worse outcomes in head and neck cancer (HNC). For an HNC cohort treated with nivolumab, CTC-positive patients had a shorter progression-free survival (PFS), and PD-L1-positive CTCs were found to be significantly associated with worse outcomes [
18]. Specifically, in gastrointestinal tumors, high PD-L1 expression on CTCs at baseline might serve as a predictor to screen patients for PD-1/PD-L1 blockade therapies, and measuring the dynamic changes in CTCs could monitor the therapeutic response [
19]. These reports indicate that a reduction in total CTC, PD-L1
posive CTC and PD-L1
high CTC counts may reflect a good response to PD-1 inhibitors (Additional file
2: Table S3). Additionally, the expression levels of MART-1, MAGE-A3 and PAX3 on CTCs have prognostic significance in patients with melanoma [
20], and these proteins are highly expressed in melanoma tissues [
21‐
25]. Multimarker RT-qPCR assay further demonstrated a significant association between the disease-free survival (DFS) and the expression levels of MART-1, MAGE-A3 and PAX3 [
20,
21].