ABSTRACT
BACKGROUND@#Pneumonectomy and sleeve resection are routine operations for the treatment of central non-small cell lung cancer (NSCLC), but some patients suffered of central NSCLC, whose pulmonary function is too poor to tolerate pneumonectomy, or the tumor involves the bronchus and pulmonary artery extensively,it is hard to perform bronchovascular sleeve lobectomy. The aim of this study is to assess the feasibility of lung autotransplantation in the treatment of central NSCLC.@*METHODS@#The clinical data of 3 cases with central NSCLC treated by lung autotransplantation was reviewed from December 2016 to December 2018. One patient underwent double sleeve resection of left upper lobe with end-to-end anastomosis of the bronchus. Because the resection of the pulmonary artery was too long to perfrom a tension-free anastomosis, the inferior pulmonary vein was cut off, then the left lower lobe was moved up for an anastomosis of the inferior pulmonary vein and the stump of the superior pulmonary vein. In the other 2 cases, left pneumonectomy was performed directly, and the upper left lobe was excised in vitro. The lower left lobe was reset to the chest after trimming and flushing and then the bronchus, pulmonary artery and pulmonary vein were anastomosed in turn.@*RESULTS@#The average operation time was 333 min, the average time of vascular occlusion was 86 min, the average blood loss was 450 mL, and the average hospital stay was 18.7 d; Perioperative complications included a case of bronchial obstruction, which improved after sputum aspiration through bronchofibroscope. The average follow-up period was 20 mon; One case died of cancer, one case had recurrence of anastomotic stoma and brain metastasis, one case had 4R lymph node metastasis (stable condition after chemotherapy), and one case survived without recurrence.@*CONCLUSIONS@#For patients with central NSCLC with extensive tumor invasion, thus inability to tolerate sleeve resection or pneumonectomy, autologous lung transplantation can preserve lung function to the greatest extent with a complete tumor resection and improve postoperative quality of life.
ABSTRACT
Objective@#To investigate the feasibility of myeloid and plasmacytoid dendritic cell combined vaccines loaded with heat-treated Lewis lung cancer cell lysates for treatment of lung cancer in mice.@*Methods@#Bone marrow cells were induced by the recombinant mouse fms-like tyrosine kinase receptor 3 ligand (rmFlt3-L) in vitro, myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) were separated by magnetic beads. The mDC, pDC, and mDC∶pDC=1∶1 were stimulated with heat-treated Lewis lung cancer cell lysates, respectively. The effects of each group on stimulating of lymphocyte proliferation and inducing of T cell to kill tumor cells in vitro were compared. The alternations of the immunophenotypes of CD80, CD86, CD40 and major histocompatibility complex Ⅱ (MHC-Ⅱ) were detected by flow cytometry. The secretion of cytokines including interlukin-12 (IL-12), interlukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA).@*Results@#The lymphocyte proliferation in mice stimulated with mDC+ pDC group loaded with heat-treated Lewis lung cancer cell lysates was 10.80±0.66, significantly higher than 8.63±0.65 of mDC group and 7.10±0.46 pDC group under the same culture conditions, respectively (P<0.05). When the ratio of effector cells: target cells (E∶T) was 10∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 31.68%±2.93%, significantly higher than 17.44%±0.97% of mDC group and 10.29%±1.33% of pDC group, respectively (P<0.05). When the ratio of E∶T was 20∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 54.77%±3.28%, significantly higher than 35.25%±1.51% of mDC group and 15.52%±0.73% of pDC group, respectively (P<0.05). When the ratio of E∶T was 40∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 73.01%±0.91%, significantly higher than 51.36%±0.58% of mDC group and 22.65%±1.28% of pDC group, respectively (P<0.05). With the rate of E∶T increased, the killing rate also increased. The mean fluorescence intensities of surface molecules including CD80, CD86, CD40 and MHC-Ⅱ of mDC: pDC=1 group pulsed with heat-treated Lewis lung cancer cell lysates were higher than those of mDC group and pDC group. The IL-6 cytokine concentrations of mDC+ pDC group, mDC group and pDC group loaded with heat-treated Lewis lung cancer cell lysates were (586.67±52.52) pg/ml, (323.33±67.14) pg/ml and (166.67±16.07) pg/ml, respectively. The concentrations of IL-12 in each group were (2 568.75±119.24) pg/ml, (2 156.25±120.55) pg/ml and (672.92±31.46) pg/ml, respectively. The concentrations of TNF-α in each group were (789.33±48.08) pg/ml, (584.89±116.49) pg/ml and (291.56±40.73) pg/ml, respectively. The concentrations of IL-6, IL-12 and TNF-α secreted by mDC+ pDC group were much higher than those of mDC group and pDC group under the same culture conditions (P<0.05).@*Conclusions@#The mDCs and pDCs combined vaccines pulsed with heat-treated Lewis lung cancer cell lysates have synergistic effects on inducing of T lymphocyte proliferation and killing tumor cells in vitro. This synergistic anti-tumor effect is related with up-regulation of co-stimulatory molecules and increased secretion of cytokines.