Prognostic value of tumor-infiltrating FOXP3 regulatory T cells in patients with hepatocellular carcinoma

Aims

CD4⁺ CD25⁺ forkhead box P3 (FOXP3)⁺ T_reg accumulate in malignant tumors and negatively regulate anti-tumor immunity. To determine the prognostic value of tumor-infiltrating regulatory T cells (T_reg), we conducted a retrospective study on 164 patients with hepatocellular carcinoma (HCC) who underwent curative hepatic resection.

Methods

We investigated the number of tumor-infiltrating FOXP3⁺ T_reg in formalin-fixed HCC specimens. The number of FOXP3⁺ T_reg for each case was calculated as the total number of positive cells per 10 high-power fields (HPF) on light microscopy. Long-term survival rate after resection according to the number of FOXP3⁺ T_reg was accessed by univariate and multivariate analyses.

Results

The mean and median numbers of tumor-infiltrating T_reg were 29.0 and 14 per 10 HPF for FOXP3⁺ T_reg. The number of FOXP3⁺ T_reg was positively correlated with preoperative serum alpha-fetoprotein levels. The disease-free survival rate was significantly lower in patients with high T_reg counts (≥14, n = 84) than in those with low T_reg counts (<14, n = 80) (13.6% vs. 25.7% at 5 years; P = 0.02). By multivariate analysis, the high T_reg counts, presence of portal vein invasion, and elevation of preoperative aspartate aminotransferase level were independent predictive factors of tumor recurrence.

Conclusions

The high number of tumor-infiltrating T_reg is an independent predictive factor of tumor recurrence after hepatic resection for HCC.     

Neoadjuvant chemo-immunotherapy modifies CD4CD25 regulatory T cells (Treg) in non-small cell lung cancer (NSCLC) patients

Background

Regulatory T cells (Treg) are critical for cancer immune evasion; whereas natural killer (NK) cells are central for effective anti-tumor immunity including antibody-induced cellular cytotoxicity (ADCC). The predictive role of Treg levels for clinical response to chemo-immunotherapy in non-small cell lung cancer (NSCLC) as well as therapy-induced Treg changes remain to be defined.

Patients and methods

The impact of Treg on NK-mediated cetuximab-dependent cellular cytoxicity was tested in vitro. Frequency and functional activity of Treg was analyzed in 31 NSCLC stage IB-IIIA patients treated by neoadjuvant Cetuximab/Docetaxel/Cisplatin prior to surgery. Data were correlated with clinical outcome variables and Treg tumor infiltration.

Results

Treg potently inhibit NK-mediated and cetuximab-induced ADCC in vitro. In addition, a significant correlation between Treg reduction and clinical response was seen. However, the grade of tumor infiltrating Treg in resected tumors did not correlate with peripheral Treg levels. Moreover, Treg levels at diagnosis did not predict clinical response to chemo-immunotherapy.

Conclusions

The drop of Treg levels during neoadjuvant chemo-immunotherapy in NSCLC patients significantly correlates with clinical response. However, Treg at diagnosis are not linked to inferior clinical response to chemo-immunotherapy in NSCLC in vivo even though Treg efficiently inhibit ADCC in vitro.     

早期非小细胞肺癌预后相关因素分析

早期非小细胞肺癌患者首选手术治疗后，仍有部分出现了局部复发和／或远处转移。筛选出预后差的患者辅以综合治疗显得尤为重要。本文分析了近年来研究的一些早期非小细胞肺癌的预后因素。     

非小细胞肺癌组织中ABCG4表达与耐药的相关性研究

目的 检测ABCG4 mRNA和蛋白在非小细胞肺癌（NSCLC）组织中的表达,分析其表达与病理类型及NSCLC细胞耐药的相关性,为研究其耐药机制提供理论基础。方法 采用免疫组化染色、RT-PCR及Western blotting检测ABCG4在NSCLC组织中的表达;MTT法检测NSCLC对化疗药物的敏感性,分析药物敏感性与ABCG4 mRNA和蛋白表达的相关性。结果 ABCG4蛋白阳性主要定位于细胞膜和胞质,其在NSCLC组织中的阳性表达率为73.9%（68/92）,而在30例癌旁正常肺组织中几乎不表达。ABCG4蛋白在肺鳞癌和肺腺癌中的阳性表达率分别为67.3%和81.4％,差异无统计学意义（P＞0.05）。环磷酰胺、吉西他滨、多柔比星、紫杉醇和顺铂在NSCLC组织中的药物敏感程度与其相应组织中ABCG4蛋白阳性表达有关（rs均＞0.3,P均＜0.05）;除紫杉醇外,环磷酰胺、吉西他滨、多柔比星和顺铂在NSCLC组织中的药物敏感程度与其相应组织中ABCG4 mRNA表达量有关（P均＜0.05）。结论 ABCG4在肺鳞癌、肺腺癌中高表达,其表达程度与NSCLC部分化疗药物耐药有关,为进一步研究ABCG4在NSCLC中的表达及可能耐药机制提供实验依据。     

Ezrin在非小细胞肺癌组织的表达及其意义

目的：探讨埃兹蛋白（Ezrin）在非小细胞肺癌（NSCLC）组织中的表达及其意义。方法：利用免疫组织化学（En Vision法）检测72例NSCLC中Ezrin蛋白的表达,分析其与NSCLC临床病理特点及其他指标之间的关系。结果：NSCLC中Ezrin蛋白的表达率为61．1％（44／72）,Ezrin高表达与患者有无区域淋巴结转移密切相关（P〈0．05）,而与患者性别、肿瘤的组织学分型、TNM分期、病理分级和吸烟等无明显相关。生存分析显示Ezrin高表达的患者生存率明显低于Ezrin低表达的患者（P〈0．05）。结论：Ezrin表达可能与NSCLC转移相关,其检测可作为判断NSCLC患者预后的一项重要指标。     

化疗联合DC-CTL治疗不同分期非小细胞肺癌的疗效分析

目的:分析化疗联合树突状细胞诱导的细胞毒性T淋巴细胞(dendritic cells and cytotoxic lymphocytes,DC-CTL)对非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的疗效及安全性.方法:收集我院2013年5月至2015年12月期间住院病理确诊为Ⅰb(具有高危因素)、Ⅱa、Ⅱb、Ⅲa、Ⅲb、Ⅳ期的NSCLC患者114例,其中接受肺癌根治术的患者分为术后化疗联合DC-CTL组20例和术后化疗组32例,未行手术患者分为化疗联合DC-CTL组23例和化疗组39例.回顾分析了114例患者的临床特点、疾病控制率(disease control rate, DCR)、中位无疾病生存期(median-disease free survival,M-DFS)、中位无进展生存期(median-progression free survival,M-PFS)、副作用等资料.随访截止至2016年11月.结果:1年DCR:术后化疗联合DC-CTL组(75.0%)vs术后化疗组(43.8%)(P=0.044).M-DFS:术后化疗联合DC-CTL组(19.5个月)与术后化疗组(11.5个月)相比,差异具有明显统计学意义(P=0.025 5).化疗联合DC-CTL治疗与化疗组相比,DCR及M-PFS不具有统计学差异.DC-CTL治疗的副作用显著低于化疗.结论:术后化疗联合DC-CTL治疗可显著提高DCR及延缓NSCLC患者的疾病进展,且安全性高.     

唑来膦酸联合放射治疗对非小细胞肺癌骨转移患者癌痛的疗效观察

目的探讨唑来膦酸联合放疗在非小细胞肺癌(NSCLC)骨转移患者癌痛治疗中的近期疗效及影响因素。方法将本院2013年5月至2015年5月收治的106例NSCLC骨转移患者随机分为联合组与对照组(n=53),对照组接受单纯放疗,联合组在放疗基础上联合唑来膦酸治疗。比较两组患者的疼痛缓解情况,采用多因素Logistic回归分析影响患者短期骨痛缓解情况的因素,单因素Logistic回归分析两种治疗方式下影响患者短期骨痛缓解的因素。结果联合组癌痛缓解有效率为92.5%(49/53),高于对照组的69.8%(37/53),差异有统计学意义(P=0.003);多因素Logistic回归分析显示治疗方式是影响NSCLC骨转移骨痛缓解情况的独立因素,差异有统计学意义(P<0.05);单因素Logistic回归分析显示联合组CT影像学表现为溶骨性病灶者的治疗效果优于对照组,且其骨相关事件发生率也低于对照组,差异有统计学意义(P<0.05)。结论唑来膦酸联合放射治疗NSCLC骨转移患者癌痛方面有较好疗效,值得临床推广。     

EGFR / HER2 / HER3 expression in tumour and gefitinib treatment in Chinese patients with advanced non-small cell lung cancer

Objective: Biological markers performable in routine practice and able to predict the clinical outcome of advanced non-small cell lung cancer (NSCLC) treated with gefitinib are urgently needed.Methods: We analyzed EGFR / HER2 / HER3 primary tumour immunohistochemical expression in a prospective and consecutive series of 90 Chinese patients.Platinumpretreated patients received a 250 mg oral dose of gefitinib once daily until disease progression; EGFR / HER2 / HER3 tumour status was related with the clinical outcome in terms of response rate (RR), time to disease progression (TTP), and overall survival (OS).Results: A high expression (scores 2-3) of EGFR, HER2 and HER3 was verified in 16.7%, 43.3% and 21.1% of tumors, respectively.EGFR and HER3 status were not significantly related with response, while the HER2 overexpression result was significantly associated with a higher RR (35.9% vs.15.7%, P = 0.027).The RR in the 13 patients with both HER2 and HER3 expression was also significantly higher than in the other 77 patients (53.8% vs.22.1%, P = 0.036).EGFR / HER2 / HER3 status was not significantly correlated with TrP or OS.Conclusion: The HER2 immunohistochemical expression can play a role in the clinical management of Chinese patients with advanced NSCLC who are candidates for gefitinib therapy     

血管内皮生长因子在非小细胞肺癌中的表达及意义

目的研究血清血管内皮生长因子(serumvascularendothelialgrowthfactor,sVEGF)与非小细胞肺癌(NSCLC)临床病理特征的关系,探讨其对NSCLC早期诊断及预后评价的意义。方法用酶联免疫法检测70例初治NSCLC患者和20例健康献血者sVEGF的含量。结果NSCLC患者sVEGF平均含量为888.4±131.8pg/ml,明显高于正常对照组的251.3±48.6pg/ml(P<0.01)。不同临床分期间sVEGF含量有显著性差异(P<0.01)。随着临床分期的进展,sVEGF含量呈上升趋势。结论sVEGF与NSCLC的发生、发展密切相关,可作为肺癌早期诊断和预后评价的一个可靠参考指标。     

重组人血管内皮抑制素联合TP和GP方案治疗晚期非小细胞肺癌31例临床观察

目的：观察重组人血管内皮抑制素（恩度）联合TP及GP方案治疗晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法：经病理学检查证实的31例ⅢB期和Ⅳ期NSCLC患者,包括鳞癌11例,腺癌18例,腺鳞癌2例,均采用恩度加常规化疗联合治疗,其中联合TP方案19例,联合GP方案12例。恩度剂量为15mg／次,加入生理盐水500ml中静滴3～4小时,第1～14天连续给药;TP方案为紫杉醇（PTX）150mg／m^2第1天,顺铂（CDDP）25mg／m^2第2—4天;GP方案为吉西他滨（GEM）1000mg／m^2第1、8天,CDDP25mg／m^2第2—4天,均为21天1周期。所有患者至少完成2个周期,根据WHO疗效评定及毒副反应分级标准,观察其近期疗效、1年生存率、疾病进展时间及毒副反应。结果：31例晚期NSCLC患者中,获得CR1例（3．2％）,PR12例（38．7％）,SD10例（32．3％）,PD8例（25．8％）,总有效率为41．9％,中位TTP为4．2个月,1年生存率为39．3％。毒副反应主要为血液学、消化道毒性等。发生Ⅲ～Ⅳ度中性粒细胞减少10例（32．3％）,Ⅲ～Ⅳ度血小板减少5例（16．1％）,Ⅲ～Ⅳ度呕吐3例（9．7％）,发生Ⅰ度及Ⅱ度血压升高各1例,肝功能损害7例,全组无心律失常及出血发生。结论：恩度联合TP及GP方案化疗治疗晚期NSCLC近期客观疗效较高,安全性好,但远期疗效仍需进一步观察。     

非小细胞肺癌术后残留放疗预后因素分析

目的 :回顾性分析非小细胞肺癌术后残留或 (和 ) N1～ 2 放疗的疗效。材料与方法 :对 1985～1993年间 2 72例 NSCLC术后残留或 (和 ) N1～ 2 患者采用 Kaplan- Meier生存曲线 ,L og- rank检验和COX多因素回归分析法探讨影响术后放疗疗效的预后因素。结果 :生存率随 N0 、N1、N2～ 3 依次明显递减(P<0 .0 5 )。姑息切除含大血管或 (和 )心包侵犯及未切者的生存率和局控率明显低于单纯切端阳性或(和 ) N1～ 2 者 (P<0 .0 1)。照射剂量 <4 0 Gy者的生存率和局控率明显低于 >4 0 Gy各组 (P<0 .0 1)。鳞癌的生存率和局控率明显高于腺癌和未分化癌 (P<0 .0 1)。结论 :病理类型、术后残留部位与切除与否以及照射剂量是影响生存率的主要因素。性别、年龄和术后放疗开始时间对预后无明显影响     

汉防已甲素对非小细胞肺癌放疗增敏作用的临床研究

目的:研究汉防已甲素(Tet)用于放疗增敏治疗非小细胞肺癌(NSCLC)的疗效及毒副反应。方法:86例NSCLC患者随机分为两组,每组43例。增敏组:在放疗第1天开始服用Tet,每次40mg,每日3次,直至放疗结束,照射方法采用常规分割外放射治疗,均采用15MVX线照射,总剂量66～70Gy/33～35f,6～7周完成。对照组:单纯放疗,方法同增敏组。结果:近期有效率增敏组为69.8%,对照组为41.9%,前者近期疗效明显提高且具有统计学差异(P<0.05);增敏组放疗期间血压、血糖、血常规、心电图、肝肾功能及常见放疗副反应等与对照组比较无显著性差异(P>0.05)。结论:Tet是安全有效的放射增敏剂,并可能减少照射剂量。     

Prognostic implication of pulmonary function at the beginning of postoperative radiotherapy in non-small cell lung cancer

PurposeThe purpose of this study was to investigate the prognostic effect of pulmonary function at the beginning of postoperative radiotherapy (PORT) in non-small cell lung cancer (NSCLC).Materials and methodsFrom January 2002 to December 2012, 115 patients with NSCLC who underwent PORT and took the forced expiratory volume in 1 second (FEV1) at the beginning of PORT were analysed. PORT began within 4–6 weeks following surgery, and the 3-dimensional conformal technique was used with conventional fractionation. The high and low FEV1 groups were divided by the median absolute value of FEV1 at the beginning of PORT, and we compared the clinical factors and survival between two groups.ResultsThe median absolute value of FEV1 at the beginning of PORT was 1.68 L (range, 0.83–3.89), and patients were divided into low and high FEV1 groups (<1.68 L versus ⩾1.68 L). Patients in the low FEV1 group showed a lower preoperative FEV1 (mean, 1.94 L versus 2.73 L, p < 0.001) and received more pneumonectomy (36.8% versus 8.6%, p < 0.001) compared to the high FEV1 group. The overall median follow-up time was 31 months (range, 3–110), and 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 52.4%, 48.9%, and 45.9%, respectively. Five-year OS of the low FEV1 group was significantly lower than that of the high FEV1 group (35.4% versus 56.9%, p = 0.002), and no significant differences were found in LRRFS and DMFS. In a multivariate analysis, the difference of OS between the low and high FEV1 groups remained significant (Hazard Ratio = 2.04, CI, 1.18–3.55, p = 0.011).ConclusionsThe FEV1 at the beginning of PORT was an independent significant prognostic factor in patients with NSCLC who received PORT. Considering this analysis was limited to only patients receiving PORT, further studies are warranted to compare the survival effect of postoperative pulmonary function between groups with/without PORT.     

非小细胞肺癌EGFR-TKIs耐药——小细胞肺癌转化的机制和治疗

肺癌是当前死亡率最高的恶性肿瘤之一。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）明显提高了晚期非小细胞肺癌（NSCLC）患者的生活质量,延长了生存期。EGFR基因优势突变的NSCLC患者临床获益明显,然而由于耐药产生,患者的中位无进展生存期（PFS）仅1年左右。最近,有文献报道EGFR TKIs耐药的机制之一是NSCLC转化为小细胞肺癌（SCLC）。本文对这种现象进行了分析总结,探讨了其转化的可能机制。根据EGFR-TKIs耐药后的处理方法和病理表型转化患者的治疗报道,探讨NSCLC EGFR-TKIs耐药后转化为SCLC患者的治疗策略。     

Prognostic value of xanthine oxidoreductase expression in patients with non-small cell lung cancer

Background

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in the purine metabolism pathway. Lack of XOR expression is associated with unfavorable clinical outcomes. The objective of this study was to correlate XOR expression with prognosis in surgically resected non-small cell lung cancer (NSCLC).

Methods

Immunohistochemical staining was performed on deparaffinized specimens from 82 patients with stage I-IV NSCLC using a polyclonal anti-XOR rabbit antibody. Cytoplasmic XOR staining was scored on frequency and intensity scales from 0 to 4 with low expression defined as 0-1 and high expression defined as ≥2-4. XOR immunostaining was correlated with clinical characteristics and outcomes and analyzed using Kaplan-Meier and Cox proportional hazard methods.

Results

Positive XOR expression was observed in 53/82 cases (65%). Patients with high XOR frequency had a longer median survival of 3053 days (95% CI: 2190-3916) vs. 592 days (95% CI: 492-692 days) for patients with low XOR frequency, p = 0.0089, HR 0.47. Neither XOR intensity nor the overall score of XOR frequency multiplied by XOR intensity demonstrated any significant association with survival. Surgical resection was performed on 61 patients of which 34 (56%) received adjuvant chemotherapy. Patients who received adjuvant chemotherapy with low XOR expression, 15/34 (44%) had a shortened median survival compared with patients who received adjuvant chemotherapy with high XOR expression (543 days vs. 2023 days, respectively, p = 0.007 and HR = 0.33).

Conclusion

Low XOR expression was associated with shortened survival and also conferred a worse prognosis for patients with NSCLC who received adjuvant chemotherapy. Further studies of the XOR pathway are warranted to validate and mechanistically explain these outcomes.     

circSMARCA5通过CCL5富集Treg细胞促进非小细胞肺癌细胞的增殖

目的：检测circSMRCA5在非小细胞肺癌（NSCLC）组织和细胞中的表达,以及其在NSCLC发生发展中的潜在功能和机制。方法：用qPCR 法检测circSMARCA5在NSCLC 组织中的表达。使用慢病毒转染法将circSMARCA5过表达质粒和对照质粒pLC5分别转染人肺癌A549 和H1975 细胞。采用qPCR法检测稳定转染细胞中circSMARCA5的表达水平。通过CCK-8、克隆形成、细胞周期和异种移植瘤实验检测circSMARCA5 过表达对A549 和H1975 细胞生物学行为的影响。通过转录组测序、KEGG和GO富集分析,确定circSMARCA5可能的靶基因。分别构建circSMARCA5过表达A549、Lewis 细胞BABL/c 裸鼠和免疫正常的C57 小鼠皮下移植瘤模型,观察circSMARCA5对裸鼠皮下移植瘤生长的影响,流式细胞术检测对Lewis 细胞移植瘤组织中Treg 细胞水平的影响。结果：circSMARCA5在NSCLC 组织中呈高表达（P<0.01）。过表达circSMARCA5可以在体外促进NSCLC 细胞的增殖（P<0.05,P<0.01）。体内实验中,circSMARCA5 可以促进裸鼠皮下移植瘤的生长（P<0.01）。机制上,经KEGG 和GO 富集分析,确定C-C 趋化因子配体5（CCL5）为circSMARCA5 的下游靶基因。过表达circSMARCA5 组A549 和H1975 细胞中CCL5 的表达量增加（均P<0.05）。circSMARCA5 介导的CCL5 上调促进了免疫正常的C57 小鼠皮下移植瘤的生长。C57 小鼠皮下移植瘤制备成的单细胞悬液行流式细胞术检测显示,circSMARCA5过表达组的Treg 细胞比例高于对照组[（3.1±0.5）% vs （1.0±0.1）%,P<0.05]。结论：circSMARCA5在NSCLC组织中呈高表达,其可能通过CCL5将Treg 细胞招募到肿瘤中,导致肿瘤的免疫逃逸,促进NSCLC的进展。     

毒黄素对非小细胞肺癌A549细胞株作用的实验研究

目的 研究毒黄素不同浓度和不同作用时间对非小细胞肺癌A549细胞增殖、凋亡和迁移的影响。方法 分别取0.5、0.375、0.25和0.125 μmol／L毒黄素作用于A549细胞（实验组）,以不加毒黄素为对照组,分别培养24 h和48 h。采用CCK-8试剂盒、Annexin V-FITC／PI凋亡试剂盒检测A549细胞增殖抑制率和凋亡率。划痕实验对比0.125 μmol／L毒黄素组和对照组（0 μmol／L毒黄素）在12、24和48 h细胞迁移率。结果 0.5、0.375、0.25和0.125 μmol/L毒黄素组24 h细胞增殖抑制率分别为（93.51±3.69）％、（40.38±3.08）％、（23.54±2.58）％和（13.07±2.37）％,48 h为（90.53±3.58）％、（53.72±3.02）％、（34.44±3.10）％和（24.78±2.43）％。0.5、0.375、0.25和0.125 μmol/L毒黄素组24 h细胞凋亡率分别为（78.68±2.22）％、（43.66±2.53）％、（20.81±2.59）％和（6.25±0.96）％,高于对照组的（1.57±0.52）％;0.5、0.375、0.25和0.125 μmol/L毒黄素组48 h细胞凋亡率分别为（88.66±3.16）％、（59.86±2.81）％、（27.89±3.48）％和（9.91±1.33）％,高于对照组的（1.59±0.55）％。0.125 μmol／L毒黄素组12、24和48 h细胞迁移率分别为7％、11％和16％,低于对照组相应的14％、26％和39％。结论 毒黄素对A549细胞有明显增殖抑制和促凋亡作用,并呈时间和剂量依赖性,且可抑制A549细胞迁移活性。     

EML4-ALK在非小细胞肺癌中的表达及临床意义

目的 探讨EML4-ALK融合基因在非小细胞肺癌（NSCLC）中的表达及其与临床病理特征的关系。方法 应用免疫组织化学SP法及组织芯片技术检测245例NSCLC及80例癌旁组织中EML4-ALK的表达情况,并分析其表达与NSCLC临床病理特征的关系。结果 EML4-ALK蛋白在NSCLC组织中的阳性表达率为7.35％（18／245）,而在癌旁组织中无表达。EML4-ALK在NSCLC中的表达与性别、吸烟史、病理类型及临床分期密切相关（P＜0.05）。结论 EML4-ALK可能在NSCLC的发生、发展过程中起到了重要作用,可作为潜在的治疗靶点。     

异长春花碱和顺铂联合异环磷酰胺治疗非小细胞肺癌的临床研究

目的：对比性研究NP方案与NIP方案治疗非小细胞肺癌的临床疗效和毒副反应。方法：24例Ⅲ～Ⅳ期非小细胞肺癌采用NP方案：NVB25mg／m^2，iv，d1.8；DDP80mg／m^2，iv，d2。23例Ⅲ～Ⅳ期非小细胞肺癌采用NIP方案：NVB25mg／m^2，iv，d1.8；DDP80mg/m^2，iv，d；IFO1．2mg／m^2，iv，d1～3。结果：NP方案组有效率45．8％，NIP方案有效率56.5％。毒副反应：剂量限制性毒性为骨髓抑制。结论：NIP方案治疗非小细胞肺癌有效率高，毒副作用能耐受。     

非小细胞肺癌的免疫治疗策略及研究进展

非小细胞肺癌（NSCLC）是一种高发病率和死亡率的恶性肿瘤。近年来以手术、放疗、化疗和靶向治疗为主的综合治疗均取得了一定进展,但晚期NSCLC患者的远期生存率仍然较低。免疫治疗主要通过特异性地增强机体的抗肿瘤免疫应答来杀伤肿瘤细胞。以免疫检查点抑制剂、抗原特异性肿瘤疫苗等为代表的多种新型免疫治疗药物在近期临床试验中显示出较好的疗效,从而使得NSCLC的治疗取得突破性进展。免疫治疗将成为NSCLC重要的治疗新模式。