BackgroundThe shaping of the tumor immune microenvironment does not only rely on tumor-infiltrating lymphocytes but on the recruitment of lymphocytes in peripheral blood. Monitoring peripheral blood lymphocyte subsets level (PBLSL) can predict treatment response and prognosis with immune checkpoint inhibitors. This study investigated the heterogeneity of PBLSL in response to chemoradiotherapy (CRT) or combined with immunotherapy (CRIT) in advanced lung cancer patients.Methods77 patients with advanced lung cancer receiving CRT or CRIT were divided into treatment-responsive and non-responsive groups based on efficacy. The study analyzed short-term efficacy and progression-free survival (PFS) according to baseline PBLSL and explored the impact under different stratifications, including treatment modality, pathology type, and age.ResultsIn all patients, higher levels of B cells, higher CD4+/CD8+ T cell ratios, and lower CD8+ T cell levels were associated with better short-term outcomes (P = 0.0035, P = 0.044, P = 0.022). Subgroup analysis revealed that in the CRT group, higher B cell levels correlated with improved efficacy (P = 0.011) and superior PFS (P = 0.048, HR = 0.3886, 95% CI = 0.1696 to 0.8902). In the CRIT group, higher CD4+ T cell levels, lower CD8+ T cell levels, and higher CD4+/CD8+ T cell ratios were linked to better efficacy (P = 0.038, P = 0.047, P = 0.017). For adenocarcinoma patients, higher CD4+/CD8+ T cell ratios and lower CD8+ T cell levels predicted better efficacy (P = 0.0155, P = 0.0119). B cell levels were significant in squamous cell carcinoma (P = 0.0291), while no PBLSL was predictive for small cell lung cancer. Among patients under 65, higher B cell levels were linked to improved efficacy and prolonged PFS (P = 0.0036, P = 0.0332, HR = 0.4111, 95% CI = 0.1973 to 0.8563). For patients over 65, differences in CD4+ T cell levels and CD4+/CD8+ T cell ratios were significant (P = 0.0433, P = 0.0338).ConclusionPBLSL predicted efficacy and prognosis in various patient stratifications, suggesting PBLSL is a reliable predictor for CRT and CRIT in advanced lung cancer. Detecting different cellular subpopulations helps identify patients with significant treatment responses across different stratifications.

Background: Immune checkpoint inhibitor (ICI) has become pivotal in the treatment of advanced lung cancer, yet the absence of reliable biomarkers for assessing treatment response poses a significant challenge. This study aims to explore the predictive value of various lymphocyte subsets in different lung cancer subtypes, thus potentially identifying novel biomarkers to improve ICI treatment stratification and outcomes. Methods: We conducted a retrospective analysis of 146 stage III or IV lung cancer patients undergoing ICI treatment. The study focused on exploring the relationship between various lymphocyte subsets and the efficacy of ICIs, aiming to determine their predictive value for post-treatment outcomes. Results: Subgroup analysis revealed a positive correlation (P=0.01) between lower CD3+CD8+T + CD8 + T lymphocyte levels and treatment response in squamous cell carcinoma patients. However, no significance was observed in lung adenocarcinoma patients. Additionally, the predictive ability of lymphocyte subsets for different immunotherapy drugs varies. In individuals receiving anti-programmed cell death ligand 1 (PD- L1) treatment, a lower CD3+CD8+ + CD8 + T lymphocyte levels is significantly associated with a positive treatment outcome (P=0.002), while there is no difference for programmed death 1 (PD-1) drugs. Among patients under 60, higher expression of CD3+CD4+ + CD4 + T lymphocytes (P=0.03) combined with lower CD3+CD8+ + CD8 + T lymphocyte levels (P=0.006) showed a statistically significant association with improved treatment response. However, in patients aged over 60, no discernible correlation was ascertained between lymphocyte subsets and therapeutic response. Through prognostic analysis, two distinct lymphocyte subsets were identified, both exerting considerable impact on progression-free survival subsequent to ICIs treatment: CD3+CD4+ + CD4 + T lymphocytes [hazard ratio (HR) =0.50, P=0.006] and CD3+CD8+ + CD8 + T lymphocytes (HR =1.78, P=0.02). Conclusions: Our findings underscore the significant heterogeneity in the predictive value of distinct lymphocyte subsets for lung cancer patients undergoing ICI treatment. These findings are particularly salient when considering various pathological types, immunotherapeutic agents, and patient age groups.

目的 探讨RICTOR对食管鳞状细胞癌细胞增殖能力的影响,分析RICTOR在食管鳞状细胞癌中的生物学功能.方法 使用cBioPortal数据库分析RICTOR表达及对肿瘤患者预后的影响.采用siRNA干扰技术分别构建食管鳞状细胞癌细胞KYSE30和KYSE150的siRNA-NC、siRNA1-RICTOR和siRNA2-RICTOR细胞,使用细胞计数试剂盒8(CCK8)和克隆形成实验检测各组细胞增殖和克隆形成能力的差异.慢病毒转染法构建KYSE30稳定敲降RICTOR的shRNA-RICTOR及shRNA-NC细胞,通过裸鼠皮下成瘤实验检测RICTOR敲降后对荷瘤小鼠移植瘤生长的影响.蛋白质印迹法检测RICTOR下游靶蛋白的表达水平,并通过体外实验初步探究RICTOR抑制剂JR-AB2-011对食管鳞状细胞癌细胞增殖的影响.结果 数据库分析结果显示,RICTOR高表达与肿瘤患者预后差相关(P=0.013).CCK8检测结果显示,敲降RICTOR基因后第96 h,在KYSE30细胞系中,与siRNA-NC(1.46±0.02)相比,siRNA1-RICTOR(0.85±0.03)和 siRNA2-RICTOR(0.70±0.03)细胞增殖能力降低,t值分别为 33.51 和 47.13,均 P＜0.001;在KYSE150 细 胞系中,与 siRNA-NC(2.37±0.10)相比,siRNA1-RICTOR(1.63±0.02)和 siRNA2-RICTOR(1.39± 0.03)细胞增殖能力也降低,t值分别为16.14和20.48,均P＜0.001.克隆形成实验结果显示,在KYSE30细胞系中,与siRNA-NC(74.00±3.26)相比,siRNA1-RICTOR(50.67±1.24)和 siRNA2-RICTOR(46.33±1.24)细胞克隆形成能力降低,t值分别为 9.44 和 11.19,均 P＜0.001;在 KYSE150 细胞系中,与 siRNA-NC(86.00±2.44)相比,siRNA1-RIC-TOR(35.33±2.05)和siRNA2-RICTOR(40.33±1.69)细胞克隆形成能力也降低,t值分别为22.41和21.66,均P＜0.001.裸鼠成瘤实验表明,在皮下接种后第5周,shRNA-RICTOR及shRNA-NC细胞成瘤后裸鼠肿瘤体积分别为(104.42±50.84)和(235.32±85.94)mm3,t=2.62,P=0.031.蛋白质印迹法检测结果显示,RICTOR 参与调控 AKT信号通路,敲降RICTOR的食管鳞状细胞癌细胞AKT Ser473位点磷酸化水平显著下调.此外,体外实验表明,RIC-TOR 的抑制剂JR-AB2-011在0.25 μmol/L浓度下培养KYSE30和KYSE150细胞72 h抑制细胞增殖,差异均有统计学意义,t值分别为39.64和28.22,均P＜0.001.结论 RICTOR可能是通过调控AKT信号通路影响食管鳞状细胞癌细胞增殖和克隆形成能力,抑制RICTOR信号通路具有潜在的抗肿瘤临床价值.

Background Two staging systems, the 8th staging system by the American Joint Committee on Cancer (AJCC) and the 11th Japanese classification by Japan Esophageal Society (JES), are currently applied in the clinic for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The differences between the two staging systems have been widely researched. However, little studies focus on the differences in specific staging between the two systems. Therefore, we aimed to compare the performance of different staging in predicting overall survival (OS) of Chinese patients with ESCC. Methods This retrospective study included 268 patients who underwent radical esophagectomy and mediastinal lymph node dissection for ESCC between January 2008 and December 2013. Patients were staged by the 8th AJCC and 11th JES staging systems. OS was estimated using the Kaplan–Meier method and compared between N stages and between stage groupings using the log-rank test. Cox proportional hazards regression analysis was performed to identify factors independently related to outcome. Further, we compared the concordance indexes (C-indexes) of the two staging systems. Results The mean age was 61.25 ± 7.056 years, median follow-up was 44.82 months, and 5-year OS rate was 47%. The OS was well predicted by the 8th AJCC N staging ( P < 0.001) and the 11th JES N staging ( P < 0.001), with a c-index of 0.638 (95% CI: 0.592–0.683) for AJCC N staging and 0.627 (95% CI: 0.583–0.670) for JES N staging ( P = 0.13). In addition, the OS was also well predicted by stage groupings of the 8th AJCC ( P < 0.001) and the 11th JES systems ( P < 0.001), with a c-index of 0.658 (95% CI: 0.616–0.699) for 8th AJCC stage grouping and 0.629 (95% CI: 0.589–0.668) for the11th JES stage grouping ( P = 0.211). Conclusions The prognostic effect of 11th JES staging system is comparable with that of AJCC 8th staging system for patients with ESCC. Therefore, both systems are applicable to clinical practice.

Objective To investigate pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) safety and efficacy in preventing hematological toxicity during concurrent chemoradiotherapy (CCRT) for small-cell lung cancer (SCLC). Methods We retrospectively assessed 80 SCLC patients treated with CCRT from January 2013 to December 2018 who received PEG-rhG-CSF within 48 hours after the end of chemotherapy, defined as prophylactic use, as the experimental group. An additional 80 patients who were not treated with PEG-rhG-CSF were matched 1:1 by the propensity score matching method and served as the control group. The main observations were differences in hematological toxicity, neutrophil changes, febrile neutropenia (FN) incidence and adverse reactions. Progression-free survival (PFS) and overall survival (OS) were analyzed with regular assessment and follow-up. Results The leukocyte, neutrophil, erythrocyte, and platelet counts and hemoglobin level decreased after CCRT, but the experimental group had slightly higher leukocyte and neutrophil counts than the control group ( P < 0.05). The incidences of grade III-IV leukopenia (18.75% vs. 61.25%) and neutropenia (23.75% vs. 67.5%) in the experimental group were significantly lower than those in the control group ( P < 0.05). The absolute neutrophil count was 4.17 ± 0.79 (× 10 9 /L) on day 1 and peaked 6.81 ± 2.37 (× 10 9 /L) on day 10 in the experimental group; the value in the control group was 2.81 ± 0.86 (× 10 9 /L) on day 1. It decreased significantly and reached the minimum 0.91 ± 0.53 (× 10 9 /L) on day 10 ( P < 0.05). The experimental group had a lower FN incidence than the control group ( P < 0.05). There was also no significant acute esophagitis or pulmonary toxicity. The treatment had no significant effect on PFS (11.4 months vs. 8.7 months, P = 0.958) or OS (23.9 months vs. 17.3 months, P = 0.325) over an 18.6-month median follow-up time. Conclusion PEG-rhG-CSF has good efficacy and safety in preventing hematological toxicity in SCLC patients during CCRT and has no significant effects on PFS or OS.

Objective:To explore the clinical factors affecting the efficacy of PD-1 monoclonal antibody in the treatment of advanced non-small cell lung cancer (NSCLC) .Methods:The clinical data of 106 patients with advanced NSCLC treated with PD-1 monoclonal antibody in affiliated Cancer Hospital of Shandong First Medical University from 2019 to 2020 were reviewed retrospectively. We evaluated the survival and analyzed the clinical influencing factors.Results:The median progression-free survival (PFS) time of the 106 patients with advanced NSCLC was 10.0 months, and the median overall survival time was not reached. The median PFS of patients receiving immunotherapy alone ( n=29) was longer than that of patients receiving immunotherapy combined with other therapies ( n=77) (13.6months vs. 8.9 months, P=0.034) . The median PFS of patients with neutrophil/lymphocyte ratio (NLR) ≤5 ( n=87) , lactic dehydrogenase (LDH) ≤245 U/L ( n=71) , and prognostic nutritional index (PNI) >45 ( n=76) before the first PD-1 immunotherapy was significantly longer than that of patients with NLR >5 ( n=19) , LDH >245 U/L ( n=35) , and PNI≤45 ( n=30) (10.3 vs. 6.1 months, P=0.008; 11.2 vs. 6.5 months, P= 0.004, 11.2 vs. 8.5 months, P=0.002) . Cox proportional risk regression model analysis showed that LDH level ( HR=0.485) and PNI index ( HR=2.160) were independent influencing factors for the prognosis of advanced NSCLC treated with PD-1 monoclonal antibody (all P < 0.05) . Conclusions:LDH level and PNI index were independent influencing factors for the prognosis of advanced NSCLC treated with PD-1 monoclonal antibody.

放射性肺损伤是胸部肿瘤放疗的常见并发症,通常包括早期的放射性肺炎和晚期的放射性肺纤维化,严重影响患者的治疗和预后.目前常用的治疗放射性肺纤维化的方法包括糖皮质激素治疗、抗炎治疗、抗氧化治疗等.随着人们对放射性肺损伤的深入研究,分子靶向治疗受到广泛关注.分子靶向抑制剂是一类新兴的治疗放射性肺损伤的药物,主要针对各类细胞因子、信号通路、酪氨酸激酶受体等靶点.本文将对放射性肺损伤的发病机制及分子靶向治疗进行系统综述.

Abstract Radiation pneumonitis is a serious side effect of thoracic radiotherapy with no established treatment currently. Anlotinib is a small‐molecule tyrosine kinase inhibitor (TKI) with anti‐angiogenic effects. The effect of TKIs in the treatment of radiation pneumonitis remains to be elucidated. We investigated whether anlotinib could alleviate radiation pneumonitis. We report a case of a patient with esophageal cancer who received anlotinib for radiation pneumonitis following radiotherapy. We also reviewed related studies to address this issue. The results in this patient suggest that anlotinib may be a valid treatment option for radiation pneumonitis.