摘要
RESUMEN Los inhibidores de la tirosina quinasa han cambiado drásticamente la perspectiva clínica de los pacientes con cáncer de pulmón de células no pequeñas avanzado con mutaciones del receptor del factor de crecimiento epidérmico. Sin embargo, existen aún retos en el manejo de los pacientes con esta mutación en un escenario metastásico, como es la resistencia intrínseca y adquirida a inhibidores de tirosina quinasa. Se discutirán los últimos avances y nuevas estrategias en primera línea de tratamiento, resistencia a osimertinib y tratamiento en mutación, en el exón 20.
ABSTRACT Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment.
摘要
Immunotherapy,represented by immune checkpoint inhibitors(ICIs),has significantly changed the treat-ment strategy of non-small cell lung cancer(NSCLC)and has become an important therapy for all stages of NSCLC.However,there is an urgent need for further clarification regarding ICIs for elderly patients with advanced NSCLC.Treatment strategies for ICIs were guided by assessing survival data of elderly NSCLC patients included in clinical trials.We concluded that treatment regi-mens such as ICI monotherapy,dual immunotherapy,and ICIs combined with chemotherapy could be carried out in elderly NSCLC patients with a performance status(PS)score<2.Elderly NSCLC patients treated with ICIs could achieve similar benefits as younger patients and are generally well tolerated.However,as age increases(especially above 80 years),the efficacy decreased and the incidence of immune-related adverse events(irAEs)gradually increased.Therefore,ICIs should be carefully selected for advanced NSCLC patients at an advanced age.Compared to age,PS was a key factor causing patients to be excluded from ICIs and poorer survival outcomes.In conclusion,immunotherapy in elderly patients with advanced NSCLC is extremely challenging,and many issues still need further exploration in this field.
摘要
AIM:To investigate the impact of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on the migration,invasion,and ferroptosis of non-small-cell lung cancer A549 cells.METHODS:The A549 cells were divided into control group,low-,medium-and high-dose(100,150 and 200 μg/mL)PHSTF groups,ferroptosis inhibitor liprox-statin-1(Lip-1)group,and high-dose PHSTF combined with Lip-1 group,each cultured in corresponding media.Cell via-bility was assessed using the CCK-8 assay,while cell migration and invasion abilities were determined through scratch and Transwell assays.Cell lipid peroxidation levels were measured using the glutathione(GSH)assay kit.RT-qPCR was em-ployed to assess the mRNA expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while Western blot was utilized to examine the protein expression of SLC7A11,GPX4,Kelch-like epichlorohy-drin-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1).RE-SULTS:Compared with control group,PHSTF significantly diminished the viability of A549 cells in a time-and dose-de-pendent manner(P＜0.01),and the cell migration and invasion were also reduced(P＜0.01),along with a significant de-crease in GSH level(P＜0.01).Treatment with PHSTF inhibited the mRNA and protein expression levels of ferroptosis-re-lated proteins,including SLC7A11 and GPX4(P＜0.01),suppressed the protein expression of Nrf2 and HO-1(P＜0.01),and enhanced the expression of Keap-1(P＜0.01).The Lip-1 partially restored the decrease in cell viability in-duced by PHSTF(P＜0.01),significantly up-regulated the protein expression levels of SLC7A11,GPX4,Nrf2 and HO-1,and suppressed the protein expression of Keap-1(P＜0.01).CONCLUSION:Total flavonoids of Pterocarya hupehen-sis Skan can inhibit the migration and invasion of non-small-cell lung cancer A549 cells,and induce the cell ferroptosis by regulating the Keap-1/Nrf2/HO-1 pathway.
摘要
Objective To compare the clinical efficacies of video-assisted thoracoscopic segmentectomy versus lobectomy for early-stage non-small cell lung cancer.Methods The clinical data of 234 patients with stage ⅠA non-small cell lung cancer and undergoing different surgical methods under video-assisted thoracoscopy admitted to Chongqing Dianjiang General Hospital were retrospectively analyzed,and the patients were divided into the lung segment group and the lung lobe group according to their surgical methods.The clinical characteristics of the patients in the two groups were balanced by a 1-to-1 ratio matching through the propensity score matching method,and each group finally included 63 cases.The perioperative indicators containing operation time,intraoperative blood loss,postoperative thoracic drainage tube indwelling time,thoracic drainage volumes 24 hours and 48 hours after operation and postoperative hospital stay were compared of patients between the two groups.The incidence of postoperative complications such as air leakage>6 days,pulmonary infection,atelectasis,hemoptysis,and hoarseness in the two groups was collected.Results There was no significant difference in the operation time,intraoperative blood loss,thoracic drainage volumes 24 hours and 48 hours after operation,postoperative thoracic drainage tube indwelling time or incidence of postoperative complications of patients between the two groups(P>0.05).The postoperative hospital stay of patients in the lung segment group was shorter than that in the lung lobe group,with statistically significant difference(P=0.003).Conclusion For patients with stage ⅠA non-small cell lung cancer,video-assisted thoracoscopic segmentectomy has similar perioperative efficacy to lobectomy,while segmentectomy has a more significant advantage in shortening the hospital stay.
摘要
AIM:To investigate the relationship between the dynamic changes of Lymphocyte-to-monocytes ratios(LMR)before PD-1 inhibitor treat-ment and the efficacy and prognosis of PD-1 inhibi-tor treatment in patients with advanced non-small cell lung cancer(NSCLC).METHODS:The clinical case data of 83 patients with advanced non-small cell lung cancer admitted to the Cancer Hospital of Wuhu Second People's Hospital from June 2019 to July 2022 were retrospectively analyzed.The rou-tine blood LMR values of all patients before and af-ter treatment were collected,the cut-off value was calculated according to the ROC curve,and the LMR was divided into two groups:high and low be-fore treatment and after treatment.The differenc-es of ORR,DCR,PFS and OS among the patients in each group were analyzed and compared,and the value of LMR value and dynamic changes after treatment on the efficacy and prognosis of patients with PD-1 inhibitors in the treatment of NSCLC pa-tients was analyzed.RESULTS:According to the ROC curve,the critical value of LMR was 1.8,and the LMR was divided into the low LMR group at baseline(LMRB/S<1.8),the high LMR group at base-line(LMRB/S≥1.8)and the low LMR group after treatment(LMRafter<1.8)and the high LMR group af-ter treatment(LMRafter≥1.8).The ORR and DCR after immunotherapy in the high LMRB/S group were high-er than those in the low LMRB/S group(P=0.037;P= 0.0025).Among the patients with low LMRB/S be-fore treatment,the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group after treatment(P=0.005).Among the patients with high LMR before treatment,the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group(P=0.034).Kaplan-Meier analysis showed that PFS and OS were longer in the high LMRB/S group than in the low LMRB/S group before treat-ment.In the low LMRB/S group before treatment,PFS and OS were longer in patients with LMRafter≥1.8 than those with LMRafter<1.8(P=0.047;P=0.007).Multivariate Cox regression model analysis showed that high LMRB/S value before treatment was an in-dependent risk factor for PFS and OS in NSCLC pa-tients(P=0.006;P=0.033).CONCLUSION:High LMR value of patients before immunotherapy may im-prove the efficacy of PD-1 inhibitors,improve the prognosis of patients,and prolong the survival time.Moreover,the increase of LMR value after treatment may increase the efficacy of patients with low LMR before treatment and improve the prognosis of patients.
摘要
Immune checkpoint inhibitors(ICIs)mainly including the CTL antigen 4(CTLA-4)and PD-1/PD-L1,which would offer a notable clinical benefit for non-small cell lung cancer(NSCLC)patients.By strengthening the antitumor immune re-sponse of the body,ICIs lead to immune-related adverse events(irAEs),including checkpoint inhibitor pneumitis(CIP).Although the clinical incidence of CIP is relatively low,some serious cases may prolong or terminate of immunotherapy,even life threateing.This article tries to summarize the clinical manifestations,pathological characteristics,biological mechanism,susceptible population,diagnosis and differential diagnosis,and integrated traditional Chinese and Western medicine treatment of CIP,in order to understand CIP more clearly.
摘要
Objective To evaluate the clinical value of free glycoprotein non-metastatic melanoma protein B(GPNMB)as a drug resis-tance and prognostic marker for non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)amplifica-tion accompanied by mutations.Methods Fifty-five cases of NSCLC patients with EGFR amplification associated with mutations who received treatment from March 2018 to September 2019 were included as the observation group.All patients received an EGFR-tyrosine kinase inhibitor(EGFR-TKI)as the first-line treatment;67 blood samples from the physical examination center during the same period were randomly included as healthy control.We compared the expression levels of free GPNMB between the two groups,explored the correlation between GPNMB expression and the clinicopathological information in the observation group;and combined the clinical efficacy to evaluate its value as a drug resistance marker.Through follow-up,the progress free survival(PFS)of patients was statistically analyzed,and through multivariate Cox regression analysis,independent risk factors affecting the survival in the observation group were explored.Results Compared with that in the control group,the expression level of free GPNMB in the observation group was signi-ficantly up-regulated.The expression level of free GPNMB in the observation group is significantly related to the clinical efficacy of EGFR-TKI(P = 0.016).Patients with high GPNMB expression have significantly stronger drug resistance,and patients with high GPNMB expression have significantly shorter PFS duration(P = 0.032).A high free GPNMB expression(HR = 4.029,95%CI:1.942-8.358,P＜0.001)is also an independent risk factor affecting patient survival.Conclusion The expression level of free GPNMB in patients with EGFR amplification accompanied by mutant NSCLC is significantly up-regulated,and its high expression is significantly related to the enhancement of the patient's drug resistance.High GPNMB expression is significantly related to the poor prognosis of patients and is an independent risk factor affecting patient survival.
摘要
Objective To explore the predictive value of CT radiomics and morphological features for the prognosis and survival in non-small cell lung cancer(NSCLC)patients.Methods The clinic data of 300 NSCLC patients(300 lesions)were downloaded from the Cancer Imaging Archive,with 210 randomly selected as the training set and 90 as the test set.According to the prognosis and survival,the patients were divided into two groups with survival period≤3 and＞3 years.3D Slicer software was used to delineate the regions of interest layer by layer in CT images,and the radiomics features were extracted from each region of interest.Both t-test and least absolute shrinkage and selection operator were utilized for radiomics feature screening.Three types of prediction models,namely radiomics model,morphological model and combined model,were constructed with Logistic regression,whose performances were evaluated using the receiver operating characteristic(ROC)curve.Results The differences in radiomics labels and mediastinal lymph node metastasis between the training set and the test set were statistically significant.For radiomics model,morphological model and combined model,the area under the ROC curve was 0.784(95%CI:0.722-0.847),0.734(95%CI:0.664-0.804)and 0.748(95%CI:0.680-0.815)in the training set,and 0.737(95%CI:0.630-0.844),0.665(95%CI:0.554-0.777)and 0.687(95%CI:0.578-0.797)in the test set,which demonstrated that radiomics model had the best diagnostic performance.Conclusion The CT radiomics model can effectively predict the prognosis and survival in NSCLC patients.
摘要
Pulmonary nodules are classified as pure ground glass nodules, part-solid nodules and solid nodules. Surgery is the main treatment for pulmonary nodules. Localization of pulmonary nodules is helpful for accurate resection. The proportion of solid component, size, pathological subtype and lymph node evaluation of pulmonary nodules are the main basis for the selection of surgical methods and the extent of lymph node dissection, but there is no unified standard at present. The management of multiple pulmonary nodules is relatively complex and often requires multidisciplinary discussion. The application of ablation technology makes the treatment of pulmonary nodules more minimally invasive. The treatment concept of pulmonary nodules is rapid recovery and overall minimal invasion.
摘要
Objective To investigate the mechanism of morin-induced autophagy in non-small cell lung cancer A549 cells based on mTOR/STAT3 signaling axis.Methods A549 cells were divided into blank group and 30,60,90,120 and 150 μg·mL-1 of morin groups.After 24,48 and 72 hours of culture,the cell proliferation activity was detected by CCK-8 method,and the cell inhibition rate was calculated.A549 cells were divided into blank group and 30,90,150 μg·mL-1 morin groups.After 14 days of culture,the cell proliferation was detected by colony formation assay.After 24 hours of culture,the cell proliferation ability was detected by BeyoClickTM EdU-488.Apoptosis was detected by flow cytometry;acridine orange staining was used to detect cell autophagy;the formation of autophagosomes was observed by transmission electron microscopy.Western Blot was used to detect the expression levels of apoptosis,autophagy and mTOR/STAT3 signaling axis-related proteins in cells.A549 cells were divided into blank group,blank group + chloroquine(10 μg·mL-1)group,morin(30,150 μg·mL-1)group,morin(30,150 μg·mL-1)+ chloroquine(10 μg·mL-1)group.After 48 hours of intervention,the cell activity was detected by CCK-8 method,and the cell survival rate was calculated.Results Compared with the blank group,the inhibition rate of A549 cells in 60,90,120,150 μ g·mL-1 of morin group was significantly increased after 24 hours of intervention(P＜0.05,P＜0.001).The inhibition rates of A549 cells in 30,60,90,120 and 150 μg·mL-1 of morin groups were significantly increased after 48 and 72 hours of intervention(P＜0.001).The number of A549 cell colonies and the number of green fluorescent proliferation positive cells in the 30,90,150 μg·mL-1 of morin groups were significantly decreased(P＜0.01,P＜0.001),the apoptosis rate was significantly increased(P＜0.01,P＜0.001),and the protein expression level of cleaved-PARP was significantly increased(P＜0.001).The protein expression levels of p-P38/P38 MAPK in A549 cells of 90 and 150 μg·mL-1 of morin groups were significantly increased(P＜0.01,P＜0.001).Different degrees of orange fluorescence appeared in A549 cells of 30,90 and 150 μg·mL-1 of morin groups,and the orange fluorescence of 90 and 150 μg·mL-1 of morin groups was significant.Autophagosomes and autolysosomes appeared in the cytoplasm of A549 cells in 150 μg·mL-1 of morin group,respectively.The protein expression of LC3-Ⅱ in A549 cells of 150 μg·mL-1 of morin group was significantly up-regulated(P＜0.05).The protein expression of Atg16L1-Ⅱ in A549 cells of 90,150 μg·mL-1 of morin group was significantly up-regulated(P＜0.001),and the protein expressions of p-mTOR/mTOR and p-STAT3/STAT3 were significantly down-regulated(P＜0.001).Compared with the morin(150 μg·mL-1)group,the survival rate of A549 cells in the morin(150 μg·mL-1)+chloroquine(10 μg·mL-1)group was significantly increased(P＜0.05).Conclusion Morin can promote the apoptosis of A549 cells and induce autophagy in A549 cells,and the mechanism may be related to mTOR/STAT3 axis.
摘要
@#Objective To investigate the clinical efficacy of multidisciplinary team (MDT) model combined with Da Vinci robot-assisted thoracic surgery in the treatment of early non-small cell lung cancer (NSCLC). Methods From July 2020 to December 2021, the patients with NSCLC who received Da Vinci robot-assisted thoracic surgery in the Department of Thoracic Surgery, General Hospital of Northern Theater Command were collected. According to whether MDT were performed before hospitalization, the patients were divided into an MDT group and a common group. The recovery and clinical efficacy were compared between the two groups. Results A total of 187 patients were enrolled, including 81 males and 106 females, aged 63 (56, 67) years. There were 85 patients in the MDT group, and 102 patients in the common group. Compared with the common group, the MDT group had lower incidence of postoperative complications (9.4% vs. 29.4%, P=0.017), shorter intraoperative operation time [55 (45, 61) min vs. 79 (65, 90) min, P<0.001], and less intraoperative blood loss [25 (20, 30) mL vs. 30 (20, 50) mL, P=0.029] in the same operation mode. In addition, the drainage volume on the second postoperative day [270 (200, 350) mL vs. 215 (190, 300) mL, P=0.004], the number of dissected lymph nodes groups [6 (5, 6) groups vs. 5 (3, 6) groups, P=0.004] and the number of dissected lymph nodes [16 (13, 21) vs. 13 (9, 20), P=0.005] in the MDT group were significantly better than those in the common group. The differences in the postoperative intubation time and postoperative hospital stay between the two groups were not statistically significant (P>0.05). Conclusion MDT combined with Da Vinci robot-assisted thoracic surgery can further reduce the risk of surgery, improve the clinical treatment effect, reduce the incidence of postoperative complications, and accelerate the rehabilitation of patients.
摘要
@#Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and is an important cause for cancer death. Although the application of immunotherapy in recent years has greatly improved the prognosis of NSCLC, there are still huge challenges in the treatment of NSCLC. The immune microenvironment plays an important role in the process of NSCLC development, infiltration and metastasis, and they can interact and influence each other, forming a vicious circle. Notably, single-cell RNA sequencing enables high-resolution analysis of individual cells and is of great value in revealing cell types, cell evolution trajectories, molecular mechanisms of cell differentiation, and intercellular regulation within the immune microenvironment. Single-cell RNA sequencing is expected to uncover more promising immunotherapies. This article reviews the important researches and latest achievements of single-cell RNA sequencing in the immune microenvironment of NSCLC, and aims to explore the significance of applying single-cell RNA sequencing to analyze the immune microenvironment of NSCLC.
摘要
@#Objective To analyze the current development of researches on biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer and to provide reference for subsequent studies. Methods Studies on biomarkers for predicting the efficacy of immunotherapy for non-small cell lung cancer indexed in the Web of Science Core Collection from 2017 to 2021 were searched by computer. The annual distribution, journals, authors, countries, institutions, and keywords of studies were visualized and analyzed by CiteSpace. Results A total of 426 studies were collected, including 298 articles and 128 reviews. The average number of published studies was about 85, and increased year by year. PD-L1 expression, tumor mutational burden, tumor microenvironment and liquid biopsy were hot keywords in this field. Conclusion In the future, combination of biomarkers in the liquid biopsy and tumor microenvironment with radiomics analysis will be the research hotspot and frontier in this field for more accurate assessment with tumor-related signatures such as lymphocytic immune status and characteristics of tumor lesions in non-small cell lung cancer patients.
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Objective To explore the correlation between the immune related adverse （irAEs） reactions in patients treated with pembrolizumab and traditional Chinese Medicine （TCM） constitution. Methods A total of 110 patients diagnosed with non-small cell lung cancer for the first time were selected. When receiving pembrolizumab immunotherapy for the first time, a general information questionnaire, a TCM constitution classification and judgment scale, an immune related adverse reaction follow-up record book, and a patient's self-perception diary were used to investigate and analyze the TCM syndrome and adverse reactions of the patients. Results Among non-small cell lung cancer patients, there were more than four TCM constitutions, with 48 cases （43.64%） having a calm constitution, 20 cases （18.18%） having a biased constitution, 30 cases （27.27%） having a yang deficiency constitution, and 12 cases （10.91%） having a yin deficiency constitution. Qi deficiency and Yang deficiency were more prone to fatigue, while Yang deficiency was more prone to rash; Qi deficiency and Yin deficiency were more prone to itching; Yang deficiency was more prone to diarrhea; Non-small cell lung cancer patients with mild constitution were less prone to immune related adverse reactions. Conclusion TCM constitution is related to irAEs, which could predict the occurrence of immune related adverse reactions from the perspective of TCM constitution and intervene in adverse reactions early.
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Objective To conduct a network meta-analysis on the effectiveness of first-line immunotherapy on patients with brain metastases from advanced non-small cell lung cancer (NSCLC). Methods Two investigators conducted a computerized search of Pubmed, Embase, Cochrane, and other databases to screen the literature, extract the information, and assess the risk of bias of the included studies. The included clinical trials were statistically analyzed using R (4.1.3) software. For the study outcome indicators OS and PFS, the risk ratios (HRs), and the 95% confidence intervals (CIs) were extracted from the included studies and logarithmically transformed into effect analysis statistics. Results Six randomized controlled trials were finally included, including 327 patients with non-excludable NSCLC brain metastases. Network meta-analysis suggested that PD-1 inhibitor + CTLA-4 was more advantageous than the conventional chemotherapy for enhancing patients’ OS (HR: 0.13, 95%CI: 0.03-0.71), followed by PD-L1 inhibitor (HR: 0.17, 95%CI: 0.04-0.74) and PD-1 inhibitor + chemotherapy (HR: 0.36, 95%CI: 0.2-0.63). PD-1 inhibitor + CTLA-4 was also more advantageous (HR: 0.37, 95%CI: 0.15-0.93) than the conventional chemotherapy for boosting patients’ PFS, followed by PD-L1 inhibitor + chemotherapy (HR: 0.44, 95%CI: 0.29-0.66) and PD-1 inhibitor (HR: 0.48, 95%CI: 0.27-0.86). Conclusion Immune checkpoint inhibitor therapy improves the survival of patients with brain metastases from advanced NSCLC. In particular, the combination of PD-1 inhibitor and CTLA-4 inhibitor show excellent survival benefit.
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ObjectiveTo explore the interaction between bruceoside B and gut microbiota and the inhibitory activity of its metabolites on human lung cancer A549 cells， and to explore the value of bruceoside B in the treatment of non-small cell lung cancer（NSCLC）. MethodBruceoside B was co-incubated with the human gut microbiota under anoxic conditions in vitro， and ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to analyze the metabolic transformation products. Cell counting kit-8（CCK-8） assay was performed to determine the effects of bruceoside B and its metabolites on the proliferation of human lung cancer A549 cells and the half inhibitory concentration（IC50） was calculated. Five healthy male rats were gavaged with bruceoside B（2 mg·kg-1） for 7 days after adaptive feeding. The feces of rats were collected before and after administration. 16S rRNA sequencing was used to assess gut microbiota. ResultBruceoside B was mainly metabolized to brusatol by human gut microbiota， the IC50 of bruceoside B and the conversion product to A549 cells were 1 755.50， 19.57 μmol·L-1， respectively， and the conversion product had a better activity at inhibiting A549 cells proliferation than bruceoside B. Additionally， The results of intestinal flora analysis showed no significant differences in α diversity and β diversity of gut microbiota after administration. In terms of species abundance， at the phylum level， bruceoside B decreased the relative abundance of Actinobacteriota and Proteobacteria， increased the relative abundance of Firmicutes， Patescibacteria and Cyanobacteria. At the genus level， bruceoside B decreased the relative abundance of Staphylococcus， Aerococcus and Psychrobacter， increased the relative abundance of Romboutsia， Lactobacillus， Clostridium sensu stricto 1， Norank-f-norank-o-Clostridia-UCG-014， Turicibacter， Allobaculum and Candidatus Saccharimonas. The results of functional prediction showed that the gut microbiota functional compositions were relatively stable. ConclusionBruceoside B can be deglycosylated by intestinal flora and converted into brusatol， with a significant increase in antitumor activity. The administration of bruceoside B will not cause significant changes in the structure and function of the intestinal flora， resulting in intestinal microecological balance disorders， and the administration appears to be beneficial to the intestinal flora of NSCLC patients.
摘要
【Objective】 To investigate the mechanism of C-C motif chemokine ligand 5 (CCL5) modulation by extracellular matrix stiffness in non-small cell lung cancer (NSCLC) and to determine the effect of CCL5 on the immunotherapy response of NSCLC. 【Methods】 The correlation between extracellular matrix stiffness and CCL5 expression in NSCLC was analyzed with the TCGA database. Polyacrylamide hydrogels with different stiffness were designed according to the extracellular matrix stiffness of NSCLC, and H1299 cells responding to the mechanical loading of hydrogel matrix stiffness were subjected to transcriptome sequencing. High matrix stiffness was verified to promote the expression of CCL5 by using sequence. 【Results】 High extracellular matrix stiffness upregulated CCL5 expression, and interferon-γ mediated signaling pathway might be involved in the process. NSCLC patients with high CCL5 expression had a greater abundance of cytotoxic T-cells in tumor tissue and reacted favorably to anti-programmed cell death protein 1 treatment. 【Conclusion】 Increased extracellular matrix stiffness promotes CCL5 synthesis, and CCL5 enhances immunotherapy responsiveness in NSCLC by increasing cytotoxic T cell infiltration in tumor tissue.
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@#Objective To explore the value of preoperative detection of soluble fragments of cytokeratin-19 (CYFRA21-1), carcinoembryonic antigen (CEA), and postoperative detection of nuclear proliferation associated antigen Ki67 in prognostic evaluation of non-small cell lung cancer patients. Methods The clinicopathological data and follow-up results of patients with non-small cell lung cancer treated in the Department of Thoracic Surgery of the First Affiliated Hospital of Xiamen University in 2017 were collected. CYFRA21-1>3.39 ng/mL was defined as positive, and CEA>5 ng/mL was defined as positive. The receiver operating characteristic curve (ROC curve) of Ki67 expression level was drawn. The maximum area under the curve (AUC) was the cutoff value of Ki67 expression level, and the Ki67 expression level greater than its cutoff value was defined as positive. Cox regression analysis was used to determine the independent risk factors for poor prognosis in patients with non-small cell lung cancer. Results Finally 248 patients were collected, including 125 males and 123 females, with a median age of 61 years (ranging from 30 to 81 years) at the time of surgery. Univariate analysis showed that positive CYFRA21-1, high expression of Ki67, positive CEA, age≥60 years at operation, distant metastasis, lymph node metastasis, maximum tumor diameter>3 cm, and TNM stage Ⅲ were associated with poor prognosis in patients with non-small cell lung cancer. When combined detection of preoperative tumor markers and postoperative Ki67, the prognosis of all negative patients was the best, and that of all positive patients was the worst. Cox regression analysis showed that positive CEA+positive CYFRA21-1+high expression of Ki67 was an independent risk factor for poor prognosis in patients with non-small cell lung cancer (P<0.05). Conclusion The combined detection of preoperative serum CYFRA21-1, CEA, and postoperative Ki67 has important value in evaluating the prognosis of non-small cell lung cancer patients.
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Immunotherapy has changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), showing great potential in the treatment of untreated and relapsed or refractory (R/R) patients. However, numerous issues that need further exploration remain with the wide application of immunotherapy. They include the exploration of biomarkers for efficacy prediction, the optimization of immunotherapy modalities, immune-related adverse effects, and the management of special populations. This review summarizes the progress of the research on immunotherapy for advanced NSCLC and discusses its challenges and future directions.
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Objective @#To investigate the regulatory effect of artemisinin derivative dihydroartemisinin ( DHA) on anti-tumor immune function of CD8 + T cells induced by non-small cell lung cancer ( NSCLC) cells . @*Methods@#NSCLC A549 cells were divided into DMSO control group and DHA treatment group . A549 cells were treated with DMSO and DHA at different concentrations (25 , 50 and 100 μmol/L) , and the optimal concentration of DHA was selected to treat A549 cells for 0 , 24 , 48 and 72 h according to half maximal inhibitory concentrate (IC50 ) . CCK 8 method and colony formation test were used to detect the effect of DHA on the proliferation and colony formation ability of A549 cells . Peripheral blood mononuclear cells (PBMCs ) of healthy individuals were isolated by density gradient centrifugation . After monocytes were removed by adhesion method , A549 cells pretreated with mitomycin C were co cultured with PBMCs at 10:1 ratio . After 2 weeks , flow cytometry was used to detect the proportion of CD8 + T cells and the expression levels of perforin and granzyme B .@*Results @#Compared with the control group , the proliferation inhibition rates of A549 cells increased after treatment with 25 , 50 and 100 μmol/L DHA for 24 h (P < 0.01) . The IC50 of DHA on A549 cells was 46.26 μmol/L. According to IC50 concentration analysis , the inhibi tion rates of A549 cells treated with 50 μmol/L DHA for 0 , 24 , 48 and 72h were 1 53% , 53.50% , 63.84% and 69.91% , and the cells inhibition rates of A548 cells increased compared with the previous ob servation time point , namely 0 , 24 and 48 h (P < 0.01) . The colony formation assay showed that the colony formation number of A549 cells in DHA treated group decreased compared with the control group (P < 0.01) . Flow cytometry results showed that compared with the control group , the proportion of CD8 + T cells induced by A549 cells in the co-culture system and the proportion of CD8 + T cells expressing perforin and granzyme B were higher in DHA pretreatment group(P < 0.01) . @*Conclusion @#DHA inhibits the growth of NSCLC cells and promotes anti tumor immune response of CD8 + T cells induced by NSCLC cells .