Beneficial effects of fetal–maternal microchimerism on the activated haplo-identical peripheral blood stem cell treatment for cancer

BackgroundPrevious studies have shown that activated haplo-identical peripheral blood stem cell (haplo-PBSC) treatment exerts an anti-tumor effect on patients with metastatic solid tumors. The purpose of this study was to test the hypothesis that fetal–maternal microchimerism enhances the beneficial effect of the haplo-PBSC treatment for cancer.MethodsTwenty-five patients with advanced-stage solid tumors refractory to standard chemotherapy were treated with haplo-PBSC donated by parents or children. Fetal–maternal microchimerism status was determined using nested polymerase chain reaction typing using sequence-specific primers (PCR-SSP). Clinical outcomes, including therapeutic response by measuring tumor size changes using CT scanning and survival times, were evaluated. The donor–recipient mixed lymphocyte response (MLR) was detected using an MTT proliferation assay. Cytokine production was determined using an ELISA method.ResultsSix patients receiving maternal–child transplants were fetal–maternal microchimerism positive (+). The mean survival time of patients with the microchimerism+ haplo-PBSC treatment was 30.17 ± 5.32 months (median 17 months), which was significantly longer than that of patients with negative (−) microchimerism (mean 16.95 ± 3.29 months, median 8 months; P = 0.043). The therapeutic response rate was significantly higher in microchimerism+ patients (83.3%) than that in microchimerism− patients (36.8%) (P = 0.047). Furthermore, suppression of donor–recipient MLR and increased production of a T-helper type 1 (Th1) type cytokine, interferon (IFN)-γ, were found in microchimerism+ patients after haplo-PBSC treatment.DiscussionThis small study suggests that fetal–maternal microchimerism is associated with a statistically significant improvement in anti-tumor effect of activated haplo-PBSC treatment. Further study is required to elucidate the mechanism for this observation.