High absolute number of naïve T cells exhibit enhanced potency and persistence in patients.
The CR/PR patients showed a high absolute number of naïve CD4+ and naïve CD8+ cells in peripheral blood. To confirm that naïve T cells played an important role in the response to CIK immunotherapy, we checked the frequencies and absolute number of T cell phenotypic markers in CIK immunotherapy patients at days 5, 10, 15, 20, 30 and 35. We found that patients with a high naïve T cell count (≥298 cells/μL in CD4+ Tn and ≥ 157 cells/μL in CD8+ Tn) maintained a higher frequency of CIK cells(CD3+CD56+) in peripheral blood after CIK cell immunotherapy (Figure 4A ). The frequency of effector-memory phenotype CIK cells (CD3+CD56+IFN-γ+) was higher in patients with high vs low naïve T cell counts (Figure 4B). However, CIK cells derived from patients with high numbers of naïve T cells exhibited a lower frequency of the immune exhaustion phenotype (CD3+CD56+PD-1+Tim-3+) compared with patients with low numbers of naïve T cells on days 5, 15 and 20 after CIK cell immunotherapy (Figure 4D). Moreover, the higher frequency of effector-memory phenotype CIK cells in high count naïve T cell patients included higher numbers of CD3+CD56+Ki67+cells on treatment days 5, 15 and 20. In summary, these findings indicated that the CIK cells harvested from patients with high absolute numbers of naïve CD4+ and naïve CD8+cells could produce more CIK cells and maintain sustained antitumor activity.