Chimeric antigen receptor (CAR) T cell shows its significant therapeutic effect in part of leukemia and lymphomas, which indicates that transgenic adoptive cellular immunotherapy may be one of the breakthroughs in treatment of solid tumors and blood diseases. The functional inhibition of CAR endogenous cells in the tumor microenvironment , molecular biology function of molecules, difficulties of CAR T cells in clinical application and the solutions , how to improve the clinical efficacy and to reduce toxic side effects for future cancer immunotherapy in clinic are reviewed in this paper.

Objective To evaluate the therapeutic effect of posterior laminectomy and transfacet discectomy combined with interbody fusion and segment fixation for the treatment of lower thoracic disc herniation.Methods From June 2000 to June 2010,36 cases of lower thoracic disc herniation were treated with method of posterior laminectomy and transfacet discectomy combined with interbody fusion and segment fixation,including 23 males and 13 females,with an average of 42 years old(range,22-61 years old).The courses of disease were from 21 days to 69 months,with an average of 22 months.The lesion locations were T10-11 for 12 cases,T11-12 for 15 cases and T12L1 for 9 cases.Each of the patients underwent X-ray and MR examination,31 of them underwent CT scanning.Twenty-five cases were central protrusion type,7 cases were para-central protrusion type,4 cases were lateral protrusionstype.The clinical results were evaluated by Otanni scored system.Results The operative time was 135-220 min,with average of 155 min.The blood loss was 350-800 ml,with average of 460 ml.All patients were successfully operated without neurological symptoms aggravation and accidents.Cerebrospinal fluid leakage occurred in 12 cases,which was treated by continuous suture or dura patch repair.Two cases with giant disc herniation suffered from muscle strength decrease of lower limbs after surgery,which gradually recovered after drug treatment of hormones,dehydration,high-pressure oxygen and nerve nutrients.Postoperative X-ray examinations showed that there were no internal fixation loosening.The followed-up period was 14 days to 48 months,mean 4 months.According to Otani scored system,there were excellent results in 12 cases,good results in 18 cases and poor results in 1 case.The clinical satisfaction rate was 83.3%.Conclusion Posterior laminectomy and transfacet discectomy combined with interbody fusion and segment fixation is a safe and effective surgical procedure for the treatment of lower thoracic disc herniation.

Objective To investigation the expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors in non-small cell lung cancer (NSCLC) and their clinical significances.Methods The serum expression levels of TRAIL in 79 cases of NSCLC and 80 cases of normal subjects were detected by enzyme-linked immunosorbent assay (ELISA).The expressions of TRAIL-R2 and TRAIL-R4 in 42 cases of NSCLC and matched normal tissues were detected by immunohistochemistry.The relationships among TRAIL,TRAIL-R2,TRAIL-R4 and clinicopathologic features of NSCLC were analyzed.Results The expression of TRAIL in NSCLC patients was lower than that in normal human [(994.3 ±293.0)ng/ml vs.(1 141.7 ±266.1)ng/ml,t =3.29,P =0.00].The expression of TRAIL was closely correlated with clinical stage (F =2.28,P =0.00) and differentiated degree (t =5.76,P =0.00).The positive expression rate of TRAIL-R2 in NSCLC was 73.8％ (31/42),significantly lower than that in the normal tissue 100.0％ (42/42) (x2 =3.88,P =0.05).The expression of TRAIL-R2 was closely correlated with clinical stage (x2 =27.89,P=0.00) and differentiated degree (x:=9.50,P =0.00).The positive expression rate of TRAIL-R4 in NSCLC was 81.0％ (34/42),significantly higher than that in the normal tissue 50.0％ (21/42) (x2 =7.34,P =0.01).The expression of TRAIL-R4 was also closely correlated with clinical stage (x2 =17.82,P =0.00) and differentiated degree (x2 =4.47,P =0.03).There was a negative correlation between the expression of TRAIL-R2 and TRAIL-R4 in NSCLC (r =-0.67,P=0.01).Conclusion The decrease of TRAIL and TRAIL-R2 and increase of TRAIL-R4 expression may promote the occurrence and development of NSCLC,and they may provide targets for clinical treatment of NSCLC.

Objective To identify the sets of lymphocytes that could systematically evaluate immune function of colorectal cancer patients, based on the expression of colorectal cancer T cells, natural killer (NK) cells, and NKT cell surface protein receptors. Methods Peripheral blood samples from 144 patients with colorectal cancer and 87 healthy controls were collected, and the differences in surface receptors of lymphocyte subsets in peripheral blood of patients and healthy controls were analyzed by means of flow cytometry and cell culture. Results Compared with healthy control group, the percentage of peripheral blood total lymphocytes, CD16^brightCD56^dimNK cells and NKT cells decreased in patients with colorectal cancer. The percentage of T cells, CD16^brightCD56^dimNK cells and NKT cell surface inhibitory receptors T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitor motif domains (TIGIT) increased; T cells, NK cells, NKT cell surface chemokine receptor C-C motif chemokine receptor 7 (CCR7) slightly decreased. Conclusion There are differences in the proportion of NK cell subsets and the expression profile of surface receptors in peripheral blood of patients with colorectal cancer.
Humans ; Lymphocyte Subsets ; Killer Cells, Natural ; Lymphocyte Count ; Receptors, Chemokine ; Colorectal Neoplasms

The laterodorsal tegmentum (LDT) is a brain structure involved in distinct behaviors including arousal, reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear. Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex (VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive (PV) GABAergic cells received preferential projections from local LDT neurons. With regard to the different subtypes of GABAergic cells, a considerable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatin-positive cells than to PV cells. Diverse inputs to the LDT on a system-wide level were revealed.