Beneficial effects of fetal-maternal microchimerism on the activated haplo-identical peripheral blood stem cell treatment for cancer.
Background Previous 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. Methods Twenty-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. Results Six 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)-gamma, were found in microchimerism(+) patients after haplo-PBSC treatment. Discussion This 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.
Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tiyuanbei, Tianjin, China.
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Ren
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Cao
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Li
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Hao
D000328:Adult; D000368:Aged; D046528:Chimerism; D016207:Cytokines / Q000276:immunology; D005260:Female; D005333:Fetus / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D011247:Pregnancy; D015996:Survival Rate; D016896:Treatment Outcome
D016207:Cytokines; D007371:Interferon-gamma