Tumor immunotherapy has emerged as a highly esteemed and rapidly evolving field in recent years,marked by the development of numerous significant therapeutic approaches. Among these,immune checkpoint inhibitors stand out as a pivotal strategy,attracting considerable attention due to their substantial research progress. This article provides a comprehensive review of the current research advancements in ten key immune checkpoints related to anti-tumor therapy,including PD-1/PD-L1,CTLA-4,LAG-3,TIM-3,TIGIT,and VISTA. By conducting an in-depth analysis of their mechanisms of action,clinical applications,and future research directions,this review aims to offer valuable insights and guidance for optimizing strategies in tumor immunotherapy.

Tumor-associated neutrophils(TANs)play a pivotal role in the immunotherapy of colorectal cancer(CRC).Within the tumor microenvironment,TANs display intricate functions,embodying both tumor-facilitating and tumor-inhibiting characteristics.TANs can be categorized into N1 type(with tumor-suppressive capabilities)and N2 type(exhibiting tumor-promoting tendencies),both of which are intimately linked to tumor progression and patient prognosis.Indicators such as the neutrophil/lymphocyte ratio(NLR)and neutrophil extracellular traps(NETs)are correlated with the prognosis of CRC.Potential targets for TANs-related immunotherapy encompass modulating their po-larization state and impeding immunosuppressive functions.The combined utilization with other immunotherapeutic mo-dalities holds the promise of augmenting the therapeutic efficacy.Notwithstanding the numerous challenges,in-depth exploration of the mechanisms underlying TANs and optimization of the treatment strategies pave novel pathways for CRC treatment in the future.

Tumor-associated neutrophils(TANs)play a pivotal role in the immunotherapy of colorectal cancer(CRC).Within the tumor microenvironment,TANs display intricate functions,embodying both tumor-facilitating and tumor-inhibiting characteristics.TANs can be categorized into N1 type(with tumor-suppressive capabilities)and N2 type(exhibiting tumor-promoting tendencies),both of which are intimately linked to tumor progression and patient prognosis.Indicators such as the neutrophil/lymphocyte ratio(NLR)and neutrophil extracellular traps(NETs)are correlated with the prognosis of CRC.Potential targets for TANs-related immunotherapy encompass modulating their po-larization state and impeding immunosuppressive functions.The combined utilization with other immunotherapeutic mo-dalities holds the promise of augmenting the therapeutic efficacy.Notwithstanding the numerous challenges,in-depth exploration of the mechanisms underlying TANs and optimization of the treatment strategies pave novel pathways for CRC treatment in the future.

Tumor immunotherapy has emerged as a highly esteemed and rapidly evolving field in recent years,marked by the development of numerous significant therapeutic approaches. Among these,immune checkpoint inhibitors stand out as a pivotal strategy,attracting considerable attention due to their substantial research progress. This article provides a comprehensive review of the current research advancements in ten key immune checkpoints related to anti-tumor therapy,including PD-1/PD-L1,CTLA-4,LAG-3,TIM-3,TIGIT,and VISTA. By conducting an in-depth analysis of their mechanisms of action,clinical applications,and future research directions,this review aims to offer valuable insights and guidance for optimizing strategies in tumor immunotherapy.

Objective To investigate the molecular mechanism of Ezrin in promoting human lung cancer metastasis.Methods The expression of Ezrin in lung cancer cell lines was detected by using RT-PCR and western blot;the cell scratch test was used to detect the effect of Ezrin on the migration ability of lung cancer cells;the mechanism of Ezrin for regulating L1CAM was detected by western blot.Results The western blot detection results showed that compared with the low metastatic lung cancer cell line H460 and EBC-1,the expression of Ezrin protein the high metastatic lung cancer cell line 95D and PC9 were higher (P＜0.05).After silencing the expression of Ezrin in 95D cells (siEzrin-95D) by using the genetic method,the cell scratch test showed that the migration ability of siEzrin-95D cells was significantly weakened compared with 95D cells (P＜0.05).Compared with 95D cells and H460 cells,after genetically silencing the Ezzin expression in 95D and H460 cells,the L1CAM expression was significantly down-regulated (P＜0.05).Conclusion Ezrin promotes lung cancer metastasis possibly by regulating the expression of L1CAM.

Objective:To determine effects of BEZ235,an inhibitor of phosphoionsitol-3-kinase (PI3K)/ mTOR,on the cell proliferation and migration in human prostate carcinoma lines including RWPE-1,PC3,and DU 145 cells.Methods:Viability of RWPE-1,PC3,and DU145 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay,while cell migration was analyzed by wound healing assay.Western blot and immunofluorescence were used to examine the changes of relevant protein expression.Results:The proliferation of PC3 and DU145 cells was effectively inhibited by BEZ235 (P<0.01),whereas RWPE-1 was not obviously inhibited.Invasion and migration of PC3 and DU145 cells were attenuated by BEZ235 via EMT pathway.Conclusion:The PI3K/mTOR dual inhibitor BEZ235 shows substantial anti-tumor activity in human prostate carcinoma lines of PC3 and DU145 cells,which may be involved in the EMT pathway.

AIM:To investigate the clinicopathological significance of the protein expression of phosphorylated ezrin at threonine 567 ( pEZRThr567 ) in lung squamous cell carcinoma, adjacent tissues and normal tissues.METHODS:pEZRThr567 protein was detected in lung squamous carcinoma, adjacent and normal tissues by the method of immunohisto-chemistry.The correlation of pEZRThr567 expression with clinicopathological parameters of lung squamous carcinomas was al-so analyzed.The localization of pEZRThr567 was detected by immunofluorescence staining in lung squamous cell line EBC-1. RESULTS:The protein expression of pEZRThr567 in lung squamous carcinoma was significantly higher than that in the adja-cent and normal lung tissues (P<0.01).pEZRThr567 mainly localized on the cell membrane, and its over-expression signi-ficantly correlated with the differentiation, clinical stage and lymph node metastasis in lung squamous carcinoma.CON-CLUSION:pEZRThr567 may be an effective biomarker for prediction of malignant potential and poor prognosis of lung cancer.

OBJECTIVETo investigate the significance of NADPH quinine oxidoreductase 1 (NQO1) protein overexpression on prognostic evaluation of head and neck squamous cell carcinoma (HNSCC).

METHODSNQO1 protein was detected in 162 of HNSCC, 45 cases of adjacent nontumor tissues and 26 samples of normal head and neck epithelia using EnVision immunohistochemical. Correlation between NQO1 overexpression and patients prognosis was also analyzed.

RESULTSThe positive rate and strongly positive rate of NQO1 protein were 84.0% (136/162) and 69.8% (113/162) in HNSCC, respectively, and both of which were significantly higher than either those in adjacent nontumor tissues and normal head and neck epithelia (both P < 0.01). NQO1 expression was significantly correlated with the clinical stage, pT and chemoradiotherapy of HNSCC (P < 0.01). Kaplan-Meier survival analysis showed that overall survival and disease-free survival rates were significantly higher in HNSCC patients with high level NQO1 expression than that those with low level of NQO1 expression (Log-rank = 6.625 , P = 0.010;Log-rank = 6.234 , P = 0.013). Additional analysis by Cox proportional hazard regression model showed that high level of NQO1 expression was an independent hazard predictor for overall survival of patients with HNSCC (Wald = 6.626, P = 0.008).

CONCLUSIONSNQO1 expression level is closely correlated with the progression and prognosis of patients with HNSCC. High level of NQO1 expression may be used as an important indicator for patients with poor prognostic HNSCC.

Breast ; enzymology ; Carcinoma, Squamous Cell ; enzymology ; mortality ; pathology ; Disease-Free Survival ; Female ; Head and Neck Neoplasms ; enzymology ; mortality ; pathology ; Humans ; Kaplan-Meier Estimate ; NAD(P)H Dehydrogenase (Quinone) ; metabolism ; NADH, NADPH Oxidoreductases ; metabolism ; Prognosis ; Proportional Hazards Models

ObjectiveTo explore the effect of different methods of drainage tube and catheter drainage in the treatment of intraventricular hematoma.MethodsThe analysis was conducted in 83 cases,who were randomly divided into two groups,the treatment group with 48 cases adopting lateral venticle catheterization combined with bulletshaped tube,and the control group with 35 cases adopting conventional catheterization.The contrasted study was conducted on the clearance rate of cerebroventricular hematoma and the effect of the different drainages.ResultsThe clearance rate in treatment group was 27.1％ ( 13/48 ),50.0％ (24/48),14.6％ (7/48),at the time of ＜ 24h,24 ～72h,＞ 72h after the operation,and 5.7 ％ ( 2/35 ),17.1％ ( 6/35 ),48.6％ ( 17/35 ) in the control group.It showed statistical significance(x2 =6.2425,9.4678,11.3757,all P ＜0.01 ).The cases with type Ⅰ of ADL stage in treatment group (47.9％)were more than control group( x2 =6.8347,P ＜0.01 ).The morbidity in treatment group was 12.5％,which was lower than control group( x2 =6.9636,P ＜0.01 ).ConclusionThe lateral venticle catheterization drainage combined with bullet-shaped tube could avoid the obstruction,reduce the morbidity,and improve the therapeutic effect.

Objective To study the surgical techniques of the extended subfrontal epidual approach to resect chordoma in skull base.Methods 18 cases of chordoma in skull base treated mierosurgically were analyzed retrospectively.Results Total resection were achieved in 15 patients(83%),gross resection in 3 patients(17%).There was no complication in all cases.Conclusion The microsurgery for chordoma in skull base via the extended subfrontal epidual approach is of the benefits such as clear and wide fields of vision,and minimize brain trauma.Lumber drain placement and the skull base reconstruction could improve the rate of total tumor removal and reduce complications.