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.