OCT4&amp;SOX2‐specific cytotoxic T lymphocytes plus programmed cell death protein 1 inhibitor presented with synergistic effect on killing lung cancer stem‐like cells in vitro and treating drug‐resistant lung cancer mice in vivo

Zhang, Xueyan; Hu, Fang; Li, Changhui; Zheng, Xiaoxuan; Zhang, Bo; Wang, Huimin; Tao, Guangyu; Xu, Jianlin; Zhang, Yanwei; Han, Baohui

doi:10.1002/jcp.27423

Cited by 14 publications

(13 citation statements)

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“…We found that patients with high SOX2 expression and high CD8+ TIL numbers demonstrated a favorable prognosis, and these constitute independent prognostic factors in LS-SCLC. SOX2-specific T-lymphocytes stimulated by CD154-activated B cells and with combined immune checkpoint inhibitors have a strong tumoricidal effect on lung cancer cell lines [32, 33]. SOX2 is also an endogenous target of T-cell immunity in non-SCLC.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of Sex-Determining Region Y-Box 2 and CD8+ Tumor-Infiltrating Lymphocytes in Limited-Stage Small-Cell Lung Cancer

et al. 2021

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Background: Sex-determining region Y-box 2 (SOX2) is a transcriptional factor that drives embryonic stem cells to neuroendocrine cells in lung development and is highly expressed in small-cell lung cancer (SCLC). However, the prognostic role of SOX2 and its relationship with tumor-infiltrating lymphocytes (TILs) has not been determined in SCLC. Herein, we assessed the expression of SOX2 and CD8+ TILs to obtain insights into the prognostic role of SOX2 and CD8+ TILs in limited-stage (LS)-SCLC. Methods: A total of 75 patients with LS-SCLC was enrolled. The SOX2 expression and CD8+ TILs were evaluated by immunohistochemistry. Results: High SOX2 and CD8+ TIL levels were identified in 52 (69.3%) and 40 (53.3%) patients, respectively. High SOX2 expression was correlated with increased density of CD8+ TILs (p = 0.041). Unlike SOX2, high CD8+ TIL numbers were associated with significantly longer progression-free survival (PFS; 13.9 vs. 8.0 months, p = 0.014). Patients with both high SOX2 expression and CD8+ TIL numbers (n = 29, 38.7%) had significantly longer PFS and overall survival (OS) compared to those from the other groups (median PFS 19.3 vs. 8.4 months; p = 0.002 and median OS 35.7 vs. 17.4 months; p = 0.004, respectively). Multivariate Cox regression analysis showed that the combination of high SOX2 expression and CD8+ TIL levels was an independent good prognostic factor for OS (HR = 0.471, 95% CI, 0.250–0.887, p = 0.02) and PFS (HR = 0.447, 95% CI, 0.250–0.801, p = 0.007) in SCLC. Conclusions: Evaluation of the combination of SOX2 and CD8+ TIL levels may be of a prognostic value in LS-SCLC.

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Section: Discussionmentioning

confidence: 99%

The Prognostic Value of Sex-Determining Region Y-Box 2 and CD8+ Tumor-Infiltrating Lymphocytes in Limited-Stage Small-Cell Lung Cancer

et al. 2021

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“…[ 49 ] The combined application of cytotoxic T lymphocytes and PD-1 inhibitor significantly decreased tumor volume and tumor weight in model mice, but promoted tumor necrosis and apoptosis compared with PD-1 inhibitor alone and blank control groups. [ 53 ] Thus, the presence of high NLR in lung cancer antagonized the therapeutic effects of PD-1/PD-L1 antibodies and resulted in the treatment failure. [ 54 ] The fact that high NLR could not predict the poor PFS for some patients receiving atezolizumab may be ascribed to their low PD-L1 expression (possible having other ligands [ 55 ] ) on neutrophils.…”

Section: Discussionmentioning

confidence: 99%

The prediction potential of neutrophil-to-lymphocyte ratio for the therapeutic outcomes of programmed death receptor-1/programmed death ligand 1 inhibitors in non-small cell lung cancer patients

Huang

Shen

2020

Medicine

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Background: Programmed death receptor-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been demonstrated to improve the prognosis of patients with advanced non-small cell lung cancer (NSCLC) compared with chemotherapy. However, there were still some non-responders. Thus, how to effectively screen the responder may be an important issue. Recent studies revealed the immune-related indicator, neutrophil-lymphocyte ratio (NLR), may predict the therapeutic effects of anti-PD1/PD-L1 antibodies; however, the results were controversial. This study was to re-evaluate the prognostic potential of NLR for NSCLC patients receiving PD1/PD-L1 inhibitors by performing a meta-analysis. Methods: Eligible studies were identified by searching online databases of PubMed, EMBASE and Cochrane Library. The predictive values of NLR for overall survival, (OS), progression free survival (PFS) and overall response rate (ORR) were estimated by hazard ratio (HR) with 95% confidence interval (CI). Results: Twenty-four studies involving 2196 patients were included. The pooled analysis demonstrated that elevated NLR before PD-1/PD-L1 inhibitor treatment was a predictor of poor OS (HR = 2.17; 95% CI: 1.64 – 2.87, P < .001), PFS (HR = 1.54; 95% CI: 1.34 – 1.78, P < .001) and low ORR (HR = 0.64; 95% CI: 0.44 – 0.95, P = .027) in NSCLC patients. Subgroup analysis revealed the predictive ability of NLR for OS and PFS was not changed by ethnicity, sample size, cut-off, HR source, study design or inhibitor type (except the combined anti-PD-L1 group); while its association with ORR was only significant when the cut-off value was less than 5 and the studies were prospectively designed. Conclusion: Our findings suggest patients with lower NLR may benefit from the use of PD-1/PD-L1 inhibitors to prolong their survival period.

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“…13 A number of studies reported that cytotoxic chemotherapy and targeted therapy kill the majority of cancer cells, except for CSCs. 32,33 Whether high expression level of Wnt5a promotes the resistance of first-generation EGFR-TKIs through CSCs need to be clarified. To improve the rationality of our hypothesis, we, in the present study, constructed a mouse xenograft model to analyze the relationship between the expression level of Wnt5a and CSCs.…”

Section: Discussionmentioning

confidence: 99%

Expression Level of Wnt5a Was Related to the Therapeutic Effects of First-Generation EGFR-TKIs

Zhang

Yang

et al. 2020

OTT

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Background and Objective: The first-generation epidermal growth factor receptortyrosine kinase inhibitors (EGFR-TKIs) have shown significant therapeutic effects on patients harboring sensitive EGFR mutations, while the mechanisms related to drug resistance have still remained elusive. This study aimed to indicate the relationship between the expression level of Wnt5a with therapeutic effects of first-generation EGFR-TKIs on lung adenocarcinoma patients harboring sensitive EGFR mutations. Methods: The medical records of 75 lung adenocarcinoma patients harboring sensitive EGFR mutations, who were admitted to our hospital and received first-generation EGFR-TKIs from June 1, 2010 to December 31, 2016, were analyzed. According to the efficacy of first-generation EGFR-TKIs, patients were divided into ineffective groups (progression-free survival (PFS) <5 months) and effective groups (PFS > 26 months). Immunofluorescence staining, immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) methods were utilized to detect the expression level of Wnt5a in the two groups. Results: Among 75 patients, 36 patients were sensitive to first-generation EGFR-TKIs (effective group) and 39 patients were resistant to first-generation EGFR-TKIs (ineffective group). The location of Wnt5a was detected by immunofluorescence staining. Immunohistochemical staining demonstrated that the expression level of Wnt5a in the ineffective group was significantly higher than that in the effective group (P=0.0216). Besides, results of RT-PCR showed that the relative expression level of Wnt5a was remarkably higher in the ineffective group than that in the effective group (P=0.0135). Conclusion: The expression level of Wnt5a was found to be associated with therapeutic effects of first-generation EGFR-TKIs in lung adenocarcinoma patients harboring sensitive EGFR mutations.

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OCT4&SOX2‐specific cytotoxic T lymphocytes plus programmed cell death protein 1 inhibitor presented with synergistic effect on killing lung cancer stem‐like cells in vitro and treating drug‐resistant lung cancer mice in vivo

Cited by 14 publications

References 42 publications

The Prognostic Value of Sex-Determining Region Y-Box 2 and CD8+ Tumor-Infiltrating Lymphocytes in Limited-Stage Small-Cell Lung Cancer

The Prognostic Value of Sex-Determining Region Y-Box 2 and CD8+ Tumor-Infiltrating Lymphocytes in Limited-Stage Small-Cell Lung Cancer

The prediction potential of neutrophil-to-lymphocyte ratio for the therapeutic outcomes of programmed death receptor-1/programmed death ligand 1 inhibitors in non-small cell lung cancer patients

<p>Expression Level of Wnt5a Was Related to the Therapeutic Effects of First-Generation EGFR-TKIs</p>

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