Dataset Information

Prognostic value of immune cells in the tumor microenvironment of early-stage lung cancer: a meta-analysis.

ABSTRACT:

Background

Early-stage non-small cell lung cancer (NSCLC) patients carry significant risk of recurrence post-surgery. In-depth characterization of the immune tumor microenvironment (TME) can have prognostic value. This study aimed to evaluate the association of individual immune cell types in the TME with clinical outcomes in surgically resected, early-stage NSCLC.

Methods

We performed a systematic literature search of the National Library of Medicine database through November 2019, investigating predefined biomarkers (CD3+ T cells, CD4+ T helper cells, CD8+ cytotoxic T cells, CD20+ B cells, CD56+ & CD57+ Natural Killer (NK) cells, CD68+ Tissue Associated Macrophages (TAMS), FoxP3+ T regulatory cells, and Mast Cells (MC)), and their association with survival following PRISMA guidelines.

Results

Studies that adjusted for important clinical covariates (such as stage and age) showed that higher levels of CD8+ cytotoxic T cells were associated with improved OS (HR = 0.68; 95% CI, 0.50-0.93) and DFS (HR = 0.60; 95% CI, 0.41-0.87), while increased CD20+ B cells (HR = 0.16; 95% CI, 0.04-0.64) and CD 56/57+ NK cells (HR = 0.50; 95% CI, 0.26-0.95) were associated with improved OS; lung cancers with increased FoxP3+ T regulatory cells (HR = 2.22; 95% CI, 1.47-3.34) had worse OS.

Conclusions

Immune cell components of the TME have prognostic value in early-stage, surgically resected NSCLC, and may reveal which patients are more likely to need additional systemic treatment, including immunotherapy. Clinical covariates need to be considered when evaluating the prognostic value of immune cells in the TME.

SUBMITTER: Tuminello S

PROVIDER: S-EPMC6935257 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prognostic value of immune cells in the tumor microenvironment of early-stage lung cancer: a meta-analysis.

Tuminello Stephanie S Veluswamy Rajwanth R Lieberman-Cribbin Wil W Gnjatic Sacha S Petralia Francesca F Wang Pei P Flores Raja R Taioli Emanuela E

Oncotarget 20191224 67

<h4>Background</h4>Early-stage non-small cell lung cancer (NSCLC) patients carry significant risk of recurrence post-surgery. In-depth characterization of the immune tumor microenvironment (TME) can have prognostic value. This study aimed to evaluate the association of individual immune cell types in the TME with clinical outcomes in surgically resected, early-stage NSCLC.<h4>Methods</h4>We performed a systematic literature search of the National Library of Medicine database through November 201 ...[more]

PMID: 31903172

Similar Datasets

Project description:IntroductionCancer progression is determined not only by the malignant behavior of tumors but also by the immune microenvironment. The tumor immune microenvironment also plays a pivotal role in determining the clinical response of non-small-cell lung cancer (NSCLC) to immunotherapies. To understand the possible mechanisms and explore new targets in lung cancer immunotherapy, we characterized the immune profiles in NSCLC patients.MethodsSeventy-one NSCLC patients who underwent radical resection were selected. The immune cell composition in paired tumor and adjacent normal lung tissues was tested by flow cytometry. The associations of tumor immune microenvironment characteristics with clinicopathological factors and overall survival were analyzed. Kaplan-Meier curves and Cox proportional hazards models were used to determine differences in survival.ResultsCompared with adjacent normal lung tissues, an increased proportion of CD45+ hematopoietic-derived cells, CD4+ T cell subtypes, Tregs and B cells was observed in tumor samples with a reduced frequency of myeloid cell populations. There was no significant increase in total CD8+ T cells, but both PD1+ and CD38+ CD8+ T cells were significantly enriched in tumor samples and statistically significantly associated with tumor size. In addition, positive CD38 expression was highly correlated with PD1 positivity. A high proportion of CD8+ T cells and a low percentage of PD1+ CD8+ T cells were statistically significantly associated with better survival in stage II and III patients, whereas a low frequency of CD38+ CD8+ T cells was statistically significantly associated with better survival in all patients and identified as an independent prognostic factor (p=0.049).ConclusionWe profiled the immune cells in the tumor tissues of NSCLC patients using flow cytometry. The results revealed significant enrichment of infiltrating immune cells. A strong correlation was identified between CD38 and PD-1 expression on CD8+ T cells in tumors. CD8+ T cells and their subtypes play a critical role in the prediction of prognosis.

Project description:BackgroundAcral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies.MethodsA total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan-Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM.ResultsThe median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25-5.29, p = 0.01; HR = 2.77, 95% CI 1.22-6.28, p = 0.02; HR = 3.43, 95% CI 1.51-7.82, p < 0.01, respectively), while patients who received post-surgical treatments had better survival (HR = 0.36, 95% CI 0.17-0.76, p = 0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications was independently associated with shorter OS in AM patients (HR = 3.61, 95% CI 1.38-9.46, p = 0.01). CD8 + T cells (p < 0.001) and M1 macrophages (p = 0.05) were more highly enriched in the invasive margin than in the tumor center. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR = 0.43, 95% CI 0.20-0.95, p = 0.03). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin (p = 0.06), which likely explains the poor prognosis in such patients.ConclusionsOur study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and tumor microenvironment profiles in AM patients and identified candidate prognostic factors, which may facilitate development of additional therapeutic options and better inform clinical management of AM patients. Based on these prognostic factors, further studies should focus on enhancing the infiltration of M1 macrophages, especially in CDK4-amplified AM patients.

Project description:Simple Summary Lung cancer is the leading cause of cancer-related deaths worldwide in part due to high rates of recurrence even with early-stage disease. This suggests that new biomarkers are needed to improve predictions for patient outcomes and better understand the underlying biology that drives poor outcomes. We believe the immune cells within the tumor microenvironment (TME) are a key differentiator between patients who are cured and patients who experience lung cancer relapse. In this study, we investigated the presence of CD14+ cells within the lung adenocarcinoma TME through immunohistochemistry and found that higher levels of CD14+ cells were correlated with shorter patient survival. In vitro studies revealed a bi-directional cross-talk between CD14+ cells and lung cancer that improved lung cancer cell recovery after chemotherapy. Our observations suggest that TME CD14+ infiltration is a prognostic marker in lung cancer and that further studies are needed to understand CD14+-cell-mediated mechanisms that influence patient outcomes. Abstract Patients with early-stage lung adenocarcinoma have a high risk of recurrent or metastatic disease despite undergoing curative intent therapy. We hypothesized that increased CD14+ cells within the tumor microenvironment (TME) could stratify patient outcomes. Immunohistochemistry for CD14 was performed on 189 specimens from patients with lung adenocarcinoma who underwent curative intent surgery. Outcomes and associations with clinical and pathologic variables were determined. In vitro studies utilized a coculture system to model the lung cancer TME containing CD14+ cells. Patients with high levels of TME CD14+ cells experienced a median overall survival of 5.5 years compared with 8.3 and 10.7 years for those with moderate or low CD14 levels, respectively (p < 0.001). Increased CD14+ cell tumor infiltration was associated with a higher stage at diagnosis and more positive lymph nodes at the time of surgery. This prognostic capacity remained even for patients with early-stage disease. Using an in vitro model system, we found that CD14+ cells reduced chemotherapy-induced cancer cell death. These data suggest that CD14+ cells are a biomarker for poor prognosis in early-stage lung adenocarcinoma and may promote tumor survival. CD14+ cell integration into the lung cancer TME can occur early in the disease and may be a promising new therapeutic avenue.

Dataset Information

Prognostic value of immune cells in the tumor microenvironment of early-stage lung cancer: a meta-analysis.

Background

Methods

Results

Conclusions

Publications

Prognostic value of immune cells in the tumor microenvironment of early-stage lung cancer: a meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets