The intrinsic potency of naïve T cells from heparinized
peripheral blood drives the response to CIK cell therapy.
T cells obtained from healthy donors and patients show variable
proportions of T-cell subsets. Both CD4+ and
CD8+ naïve cells (Tn) comprised a proportionately
higher absolute number of healthy donor compared with patients (298
cells/μL vs. 156 cells/μL, p < 0.001, for
CD4+Tn, and 157 cells/μL vs. 56 cells/μL, p
< 0.001, for CD8+Tn). When there was only
higher percentage of healthy donor compared with patients in
CD8+ naïve cells (44.6% vs. 17.5%, p <
0.001) (Figure 3A and 3B). We next compared the proliferation of CIK
cells from healthy donors and patients of absolute number of naïve
CD4+ and naïve CD8+ cells in
peripheral blood. We found that T cells from healthy donors exhibited a
significantly greater proportion of naïve T cells compared to patients
(Figure 3C and 3D). To understand whether CIK cells amplified from
healthy donors with high naïve T cell counts had more activity and
cytotoxicity. The proliferation of CIK cells that was associated with
progressive differentiation during 15 days culture in vitro , and
the number of T cells displaying an immune exhaustion phenotype such as
CD3+PD-1+Tim-3+were significantly increased in samples from patients, but not in
samples from healthy donors (Figure 3E ). However the percentage of
proliferating CIK cells
(CD3+CD56+Ki67+)
from healthy donors was significantly greater than patients (Figure 3F).
Moreover, cytotoxicity assays found that the in vitro cytolytic
activity of CIK cells after amplification was higher in the samples from
healthy donors than in samples from patients (Figure 3G). In our study,
the frequency of naïve T cell in the patients with CR/PR were higher
then in PD or SD. To determine if the higher proliferation rate and
cytotoxicity of CIK cells amplified from patients with CR/PR could be
maintained as long-term persistent immune activity, we checked the
frequency and absolute numbers of naïve CD4+ and
CD8+ cells in peripheral blood after 1 and 2 weeks
transfer immunotherapy. Our results showed that PR/CR patients
maintained the high level of CIK cells
(CD3+CD56+) (Figure 3H and 2I) and
IFN-γ -producing CIK cells
(CD3+CD56+IFN-γ+)
(Figure 3J and 3K) in peripheral blood. In summary, these findings
indicated that patients with high absolute number of naïve
CD4+ and naïve CD8+ cells could
produce more CIK cells which likely play an important role in CIK
immunotherapy.