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.