Cisplatin pretreatment enhances anti-tumor activity of cytokine-induced killer cells

AIM： To investigate whether cisplatin （DDP） enhances the anti-tumor activity of cytokine- induced killer （CIK） cells in a murine colon adenocarcinoma model. METHODS： Tumor size and weight served as indicators of therapeutic response. Immunohistochemistry was performed to observe intratumoral lymphocyte infiltration and tumor microvessel density. Changes in the percentage of regulatory T （Treg） cells within the spleens of tumor-bearing mice preconditioned with DDP were monitored using flow cytometry. RESULTS： A marked T cell-dependent, synergistic anti- tumor effect of the combined therapy was observed （1968 ± 491 mm3 ys 3872 ＋ 216 mm3; P = 0,003）, Preconditioning chemotherapy with DDP augmented the infiltration of CD3＋ T lymphocytes into the tumor mass and reduced the percentage of both intratumoral and splenic Treg cells. CONCLUSION： Preconditioning with DDP markedly enhances the efficacy of adoptively transferred CIK cells, providing a potential clinical modality for the treatment of patients with colorectal cancer.

Utility of co-transplanting mesenchymal stem cells in islet transplantation

Islet transplantation is characterized by the transplantation of isolated islets from donor pancreata into a diabetic recipient. Although it is a viable choice in the treatment of insulin dependent diabetes mellitus, most patients (approximately 90%) require insulin five years after transplantation. Recently, the co-transplantation of mesenchymal stem cells (MSCs) and islets in animal studies has revealed the effectiveness of MSCs co-transplantation for improving islet function. Themechanisms underlying the beneficial impact of MSCs include immunomodulation and the promotion of angiogenesis. In this review, we discuss MSCs and how they support improved graft survival and function.

Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice

Background Immunosuppressive regulatory T cells （Tregs） participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change leads to a higher incidence of tumors in the elderly. To this end, we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 （FoxP3） in the aging process and its relationship with lung tumors in humans and mice. Methods The percentage of CD4＋CD25＋CD127lowTregs and expression of FoxP3 mRNA were analyzed using flow cytometry （FCM） and real-time fluorescence-based quantitative polymerase chain reaction （FQ-PCR）. Markers were analyzed in the peripheral blood （PB） of 65 elderly patients （age 〉-65 years） with primary non-small cell lung cancer （NSCLC）, 20 younger patients （aged 〈55 years） with NSCLC, 30 elderly healthy individuals and 30 young healthy individuals. Furthermore, we set up the Lewis lung cancer model with C57BL/6 female mice. Thirty-six mice were divided into a young healthy group, a middle-aged healthy group, tumor group, and an elderly tumor group. The percentage an elderly healthy group, a young tumor group, a middle-aged of CD4＋CD25＋FoxP3＋ Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups. Results The percentage of peripheral CD4＋CD25＋CD127low Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals. Further analysis showed that the percentage of CD4＋CD25＋CD127lowTregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis （TNM） staging in elderly patients with NSCLC. In the mouse model, the percentage of CD4＋CD25＋FoxP3＋ Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups, with the highest expression in the elderly tumor group. In the healthy groups, the elderly healthy mice had the highest percentage of Tregs and expression of FoxP3 mRNA. The elderly mice had larger and heavier tumors than did the young and middle aged mice. Conclusions The up-regulation of Tregs and the FoxP3 gene with aging may play an essential role in oncogenesis and development of lung tumors in an elderly population.