scholarly journals 3363 Prognostic Value of Immune-Related Biomarkers in Resected Non-Small Cell Lung Cancer

2019 ◽  
Vol 3 (s1) ◽  
pp. 153-153
Author(s):  
Rajwanth R Veluswamy ◽  
Stephanie Tuminello ◽  
Francesca Petralia ◽  
Wil Lieberman-Cribbin ◽  
Pei Wang ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Meta Analysis ◽  
Stage I ◽  
Resected Stage ◽  
Iiia Nsclc ◽  
Nsclc Patients ◽  
Lung Adenocarcinomas ◽  
The Impact

OBJECTIVES/SPECIFIC AIMS: Immune cells within the tumor microenvironment (TME) play an important role in the development and progression of non-small cell lung cancer (NSCLC). However, data evaluating the impact of individual immune cell types on NSCLC outcomes is limited and often conflicting. We performed a meta-analysis of existing data and used The Cancer Genome Atlas (TCGA) to evaluate the effect of several immune cells on surgical outcomes of stage I-IIIA NSCLC. METHODS/STUDY POPULATION: PubMed was searched to identify eligible studies evaluating survival of surgically resected stage I-IIIA NSCLC patients according to immune cell infiltration. Meta-analysis was performed using a linear mixed-effects model to determine overall, disease specific and progression free survival. We then used a similar patient subset found in the TCGA to validate the meta-analysis findings. For the TCGA analysis, sample-specific scores for different immune cells were computed via xCell using level three RNAseq data. After stratifying the cohort by histologic subtype, the association between each cell type and survival was assessed via Cox Regression, while adjusting for stage, gender and smoking status. RESULTS/ANTICIPATED RESULTS: From the meta-analysis (37 articles eligible; N = 8,162 patients), high levels of CD20+ B cells (hazard ratio [HR]: 0.36, 95% confidence interval [CI]: 0.15-0.85), natural killer (NK) cells (HR: 0.64, 95% CI: 0.41-1.0), and dendritic cells (0.34, 95% CI: 0.13-0.84) were significantly associated with better overall survival (OS); T regulatory cells (HR: 1.85, 95% CI: 1.35-2.54) were associated with worst OS. High CD8+ T cell infiltrates were associated with improved disease-free survival (DFS; HR: 0.85, 95% CI 0.73-0.99), while CD68+ macrophages (HR> 2.83, 95% CI: 1.28-6.24) were associated with worst DFS. In the TCGA cohort, lung adenocarcinomas rich in CD4 T cells, CD8 T cells, B cells, and NK cells were associated with improved OS in unadjusted analysis. In adjusted analysis, only NK cells were associated with improved OS (HR: 0.82, 95% CI: 0.69-0.98). There was no significant association of any immune cell type for DFS in lung adenocarcinomas and with both OS and DFS in Squamous Cell Lung Cancers (p>0.05 for all comparisons). DISCUSSION/SIGNIFICANCE OF IMPACT: The presence of tumor infiltration by specific immune cell subsets may potentially predict survival outcomes in resected stage I-III NSCLC patients. However, the impact of immune cells may not be similar in all histologic types and after adjusting for important clinical confounders.

scholarly journals When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Katrin Schlie ◽  
Jaeline E. Spowart ◽  
Luke R. K. Hughson ◽  
Katelin N. Townsend ◽  
Julian J. Lum
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Patient Treatment ◽  
Low Oxygen ◽  
Tumor Environment ◽  
And Function ◽  
The Impact

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism. Autophagy upregulation in cancer cells liberates nutrients, decreases the buildup of reactive oxygen species, and aids in the clearance of misfolded proteins. Together, these features impart a survival advantage for cancer cells in the tumor microenvironment. This observation has led to intense research efforts focused on developing autophagy-modulating drugs for cancer patient treatment. However, other cells that infiltrate the tumor environment such as immune cells also encounter hypoxia likely resulting in hypoxia-induced autophagy. In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system.

scholarly journals Evaluation of Different Treatment Strategies Between Right-sided and Left-sided Pneumonectomy for Stage I-IIIA Non-small Cell Lung Cancer Patients

2020 ◽  
Author(s):  
Bo Jia ◽  
Qiwen Zheng ◽  
Jianjie Li ◽  
Jun Zhao ◽  
Meina Wu ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Treatment Strategies ◽  
The United States ◽  
Stage I ◽  
Cancer Specific Survival ◽  
Lung Cancer Patients ◽  
Propensity Score Matching Analysis ◽  
Appropriate Treatment ◽  
Iiia Nsclc ◽  
Nsclc Patients

Abstract BackgroundThis study aimed to assess the different survival outcome of stage I-IIIA NSCLC patients who received right-sided and left-sided pneumonectomy, and to further develop the most appropriate treatment strategies. MethodsWe accessed data from the Surveillance, Epidemiology, and End Results database in the United States for the present study. An innovative propensity score matching analysis was used to minimize the variance between groups.ResultsFor 2,683 patients who received pneumonectomy, cancer-specific survival (HR=0.863, 95%CI: 0.771 to 0.965, P=0.010) and overall survival (OS) (HR=0.875, 95%CI: 0.793 to 0.967, P=0.008) were significantly superior of left-sided pneumonectomy compared with right-sided pneumonectomy. Cancer-specific survival (HR=0.847, 95%CI: 0.745 to 0.963, P=0.011) and OS (HR=0.858, 95%CI: 0.768 to 0.959, P=0.007) were also significantly longer with left-sided over opposite-sided pneumonectomy after matching analysis for 2,050 patients. Adjuvant therapy could significantly prolong cancer-specific survival (67 versus 51 months, HR=1.314, 95%CI: 1.093 to 1.579, P=0.004) and OS (46 versus 30 months, HR=1.458, 95%CI: 1.239 to 1.715, P<0.001) among left-sided pneumonectomy patients after matching procedure. While adjuvant therapy did not increase cancer-specific survival for right-sided pneumonectomy patients (46 versus 42 months, HR=1.112, 95%CI: 0.933 to 1.325, P=0.236). Subgroup analysis showed that adjuvant chemotherapy could significantly improve cancer-specific survival and OS for all pneumonectomy patients. But radiotherapy was associated with worse survival for patients with right-sided pneumonectomy. ConclusionsPneumonectomy side could be deemed as an important factor when physicians choosing the most optimal treatment strategies.

scholarly journals Impact of Lymphadenectomy on the Oncologic Outcome of Patients with Adrenocortical Carcinoma—A Systematic Review and Meta-Analysis

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 291
Author(s):  
Anne Hendricks ◽  
Sophie Müller ◽  
Martin Fassnacht ◽  
Christoph-Thomas Germer ◽  
Verena A. Wiegering ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adrenocortical Carcinoma ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Postoperative Mortality ◽  
Length Of Hospital Stay ◽  
Oncologic Outcome ◽  
Stage I ◽  
Tumor Stages ◽  
The Impact

(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I–III) and those including all tumor stages (I–IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001–2020, and 5 were included in the meta-analysis. Three studies (N = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I–III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95% confidence interval (95% CI): 0.26–0.68). Based on results of studies including patients with ACC stage I–IV (2 studies, N = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95% CI: 0.70–1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I–III).

scholarly journals Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Claire Healy ◽  
Natalia Munoz-Wolf ◽  
Janné Strydom ◽  
Lynne Faherty ◽  
Niamh C. Williams ◽  
...  
Keyword(s):  
Immune System ◽  
Trace Metals ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Immune Cells ◽  
Immune Cell ◽  
Redox Activity ◽  
Nutritional Immunity ◽  
Airway Microbiome ◽  
The Impact

AbstractNutritional immunity is the sequestration of bioavailable trace metals such as iron, zinc and copper by the host to limit pathogenicity by invading microorganisms. As one of the most conserved activities of the innate immune system, limiting the availability of free trace metals by cells of the immune system serves not only to conceal these vital nutrients from invading bacteria but also operates to tightly regulate host immune cell responses and function. In the setting of chronic lung disease, the regulation of trace metals by the host is often disrupted, leading to the altered availability of these nutrients to commensal and invading opportunistic pathogenic microbes. Similarly, alterations in the uptake, secretion, turnover and redox activity of these vitally important metals has significant repercussions for immune cell function including the response to and resolution of infection. This review will discuss the intricate role of nutritional immunity in host immune cells of the lung and how changes in this fundamental process as a result of chronic lung disease may alter the airway microbiome, disease progression and the response to infection.

Efficacy of KD033, an anti-human-PD-L1-IL-15 bispecific protein, in human-PD-L1 positive and negative murine tumor models.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14556-e14556
Author(s):  
Stella Martomo ◽  
Dan Lu ◽  
Zhanna Polonskaya ◽  
Xenia Luna ◽  
Zhikai Zhang ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Tumor Growth ◽  
Nk Cells ◽  
Immune Cell ◽  
Clinical Stage ◽  
Tumor Models ◽  
T Cell Infiltration ◽  
Negative Tumor ◽  
Tumor Expression ◽  
The Impact

e14556 Background: KD033 is a clinical-stage bispecific fusion molecule consisting of a high-affinity anti-human-PD-L1 antibody and human IL-15. Preclinical studies have demonstrated that targeting IL-15 with anti-PD-L1 antibody resulted in increased efficacy, safety and maximal tolerated dose of the fusion protein compared to administration of free IL-15, as well as reduction of tumor growth in both PD-L1 positive and negative tumor models (1). The goal of the current study is to directly compare KD033 efficacy when PD-L1 is present or absent on the surface of the same tumor. Methods: KD033 was administered in the human-PD-L1/PD-1 transgenic C57/Bl6 mice subcutaneously transplanted with human-PD-L1 positive and negative MC38 colon carcinoma cells. This animal model allowed the evaluation of the impact of the presence or absence of human-PD-L1 expression on the tumor cell surface without altering human-PD-L1 expression on immune cells. Results: KD033 treatment resulted in significant tumor growth reduction in both human-PD-L1 positive and negative MC38 tumors. Analysis of peripheral immune cell populations showed similar increases of CD8 T and NK cells between human-PD-L1 positive and negative MC38- bearing mice after KD033 administration. Immunohistochemistry demonstrated a significant increase in CD8 T-cell infiltration into the human-PD-L1 positive MC38 tumors, whereas NK cells infiltration was more pronounced in the human-PD-L1 negative MC38 tumors. Analysis of tumor gene transcription after KD033 treatment highlighted differences in gene signatures between human-PD-L1 positive and negative MC38 tumors following KD033 treatment. Conclusions: These results showed that the efficacy of anti-PD-L1-IL-15 fusion protein is not limited to PD-L1 tumor expression as KD033 was efficacious in both PD-L1 positive and negative tumors. Mol Cancer Ther February 1 2021 (20) (2) 347-356; DOI: 10.1158/1535-7163.MCT-20-0457

Impact of BRAF mutations on prognosis and immunotherapy response in microsatellite instability/mismatch repair deficient metastatic colorectal cancer: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3557-3557
Author(s):  
Robin Park ◽  
Laércio Lopes da Silva ◽  
Sunggon Lee ◽  
Anwaar Saeed
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Braf Mutation ◽  
Meta Analysis ◽  
Stage Iv ◽  
Stage I ◽  
Prognostic Impact ◽  
Braf Mutations ◽  
Mutation Status ◽  
The Impact

3557 Background: Mismatch repair deficient/microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC) defines a molecular subtype with distinct clinicopathologic characteristics including an excellent response to immunotherapy. Although BRAF mutations are established as a negative prognostic marker in CRC, whether they retain their negative prognostic impact in or alter the response to immunotherapy in dMMR/MSI-H CRC remains unknown. Herein, we present a systematic review and meta-analysis of the impact of BRAF mutations on the overall survival (OS) and immune checkpoint inhibitor (ICI) response in dMMR/MSI-H CRC. Methods: Studies published from inception to 26 January 2021 were searched in PubMed, Embase, and major conference proceedings (AACR, ASCO, and ESMO). Eligible studies included the following: 1) observational studies reporting outcomes based on BRAF mutation status in dMMR/MSI-H CRC patients and 2) experimental studies of ICI reporting outcomes based on BRAF mutation status in dMMR/MSI-H CRC patients. A summary hazard ratio (HR) was calculated for OS in BRAF mutated ( BRAFmut) vs. BRAF wild type ( BRAFwt) patients (pts) with the random effects meta-analysis (REM). A summary odds ratio (OR) was calculated for objective response rate (ORR) in BRAFmut vs. BRAFwt pts treated with ICI with the REM. Results: Database search conducted according to PRISMA guidelines found 4221 studies in total. Initial screening identified 30 studies and after full-text review, 9 studies (N = 4158 pts) were included for the meta-analysis of prognosis (analysis A) and 3 studies (N = 178 pts) were included for the meta-analysis of ICI response (analysis B). The outcome measures are summarized in the table below. Analysis A showed that in stage I-IV dMMR/MSI-H CRC pts, BRAFmut was associated with worse OS than BRAFwt (HR 1.57, 1.23-1.99). The heterogeneity was low (I2 = 21%). Subgroup analysis showed no significant difference in the prognostic impact of BRAF mutation status between stage IV only and stage I-IV CRC pts. Analysis B showed no difference in ORR (OR 1.04, 0.48-2.25) between BRAFmut vs. BRAFwt dMMR/MSI-H pts who received ICI. The heterogeneity was low (I2 = 0%). Conclusions: BRAF mutations retain their negative prognostic impact in dMMR/MSI-H stage I-IV and stage IV CRC but are not associated with differential ICI response. Limitations include the following: analysis A was based on retrospective studies; also, the impact of BRAF status on the survival outcome of ICI could not be assessed due to limited number of studies.[Table: see text]

scholarly journals Mitosis in Cancer Cell Increases Immune Resistance via High Expression of HLA-G and PD-L1

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2661
Author(s):  
Matti Ullah ◽  
Warda Aoudjeghout ◽  
Cynthia Pimpie ◽  
Marc Pocard ◽  
Massoud Mirshahi
Keyword(s):  
Protein Expression ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
G1 Phase ◽  
G2 Phase ◽  
The Impact

Cancer is a result of “aggressive” division and uncontrolled proliferation of the abnormal cells that survive attack by immune cells. We investigated the expression of HLA-G and PD-L1 with the different stages of cancer cell division along with their role in the interaction of immune cells in vitro. Ovarian cancer (OVCAR-3) and chronic myeloid leukemia cell line (K-562) are used for this study. The correlation of protein expression with percentage of cells in each phase (G1, S and G2 phase) was evaluated through FACS. Cells were synchronized in G1, G2 and mitotic phase to evaluate gene (RT-qPCR) and protein expression (FACS). Real-time immune cell attack (RTICA) analysis with PBMCs (peripheral blood mono-nuclear cells) and cancer cells were performed. We found that cells expressing higher levels of HLA-G and PD-L1 are mainly in G2 phase and those expressing lower levels are mainly in G1 phase. Evidently, the higher expression of the two proteins was observed when synchronized in mitotic phase as compared to low expression when synchronized in G1 phase. RTICA analysis showed the presence of HLA-G delayed the lysis of the cells. In conclusion, the cancer cell can escape from immune cells in division stage that suggests the impact of mitosis index for cancer immunotherapy.

Impact of gemcitabine (G) on the activity of first-line chemotherapy in non-small cell lung cancer (NSCLC): A meta-analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7138-7138
Author(s):  
G. L. Pappagallo ◽  
O. Belvedere ◽  
O. Vinante ◽  
F. Grossi
Keyword(s):  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Response To Treatment ◽  
Third Generation ◽  
First Line ◽  
Significant Difference ◽  
Nsclc Patients ◽  
The Impact ◽  
Line Chemotherapy

7138 Background: A two-drug platinum-based regimen in which cisplatin or carboplatin is combined with a third-generation agent (i.e. paclitaxel, vinorelbine, docetaxel, or G) is the standard first-line treatment for NSCLC patients with good performance status. Encouraging results have recently been reported for nonplatinum regimens composed of two third-generation drugs. Methods: To assess the impact of G on the activity of first-line chemotherapy in NSCLC, we carried out a meta-analysis on data from 4,362 NSCLC patients who were enrolled in 11 randomized trials comparing a G-containing vs. G-free new generation regimens. We constructed 2x2 tables using response to treatment data. For trials with more than one eligible G-free comparator arm, individual comparisons between the G-based treatment arms and each of the comparator arms were analyzed. A general variance-based method was used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). We assessed for heterogeneity among the trials based on standard methods. Results: Sixteen comparisons contributed to this analysis. G-containing regimens included: G+cisplatin (894), G+docetaxel (565), G+paclitaxel (200 patients), G+vinorelbine (157), G+carboplatin (49). G-free regimens included: vinorelbine+cisplatin (866), carboplatin+paclitaxel (539), docetaxel+cisplatin (494), cisplatin+paclitaxel (439), vinorelbine+carboplatin (159). Comparing G-containing vs. G-free regimens, the OR for progression was 0.867 (CI 95% 0.770–0.977; p = 0.019), with heterogeneity chi-square 11.639 (p = 0.71). No significant difference was observed for complete (OR 0.909, CI 95% 0.556–1.487; P = 0.707) and overall (complete + partial) response (OR 0.987, CI 95% 0.881–1.106; P = 0.819). Conclusions: These data demonstrate that the progression of disease is more likely in patients treated with G-free doublets. Further analyses are required to address whether disease control (objective response + stable disease) is associated with a survival benefit and may therefore be used as a surrogate end point for survival in chemotherapy trials of NSCLC. No significant financial relationships to disclose.

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