Patients with a high frequency of naïve T cells in circulating blood have better responses to CIK immunotherapy.
To identify the specific factors in heparinized peripheral blood that predict why only certain patients have strong responses to CIK treatment, we studied 68 patients with advanced solid tumors (including 42 lung cancers, 14 liver cancers, nine colon cancers and three renal carcinomas) who received activated autologous CIK cell treatment (Figure 1). The patient clinical characteristics are shown in Table 1. As shown in our data, efficacy of treatment was not related to patient age, prior therapy, peripheral tumor burden, tumor histology, ECOG PS or other typical factors (Table 1). We first tested the frequency of 11 leucocyte subsets in the heparinized peripheral blood of patients before CIK treatment. The absolute and proportional medians of the 11 leucocyte subsets in different clinical responses are presented in Table 2. As shown in the hierarchical clustering of partial subsets of proportional data across all samples analyzed in a heatmap representation, we divided the patient into three clusters of PD, SD and CR/PR. Naïve CD4+ and CD8+ T cells subsets contributed to the separation with higher frequencies (marked in green) observed in samples from CR/PR patients, whereas samples from PD individuals contained fewer proportions (Figure 2A). The naïve CD4+ and CD8+ T cell subsets were identified by surface markers: CD4+CD45RA+ CCR7+CD62L+ and CD8+CD45RA+ CCR7+CD62L+, respectively (Figure 2B and 2C). The patients who attained PR or CR by CIK therapy had higher absolute numbers of naïve CD4+ and CD8+ T cells in heparinized peripheral blood (naïve CD4+ means: PD vs SD vs CR/PR = 73 vs 108 vs 202; naïve CD8+ means: PD vs SD vs CR/PR = 31 vs 62 vs 90) (Figure 2D and 2F). The frequency and absolute number of naïve CD4+ T cells were significantly higher in the subset of patients who reached CR/PR than in PD or SD patients after CIK therapy (Figure 2E and 2F). Moreover, the absolute number of naïve CD8+ cells was also higher in the subset of patients who reached CR/PR than in PD or SD patients, but the frequency were no statistical differences between CR/PR patients and PD/SD patients(Figure 2E and 1F). To summarize, our results indicated that patients who reached CR/PR after CIK therapy had higher absolute numbers of naïve CD4+ and naïve CD8+T cells.