Abstract
Tumor-infiltrating immune cells are a pivotal component of the tumor microenvironment (TME), but their indicative role remains poorly defined. A meta-analysis was performed to reveal the prognostic efficiency of tumor-infiltrating immune cells in gastric cancer (GC). By searching PubMed and Embase, we identified a total of 35 eligible articles that involved 4888 patients. Random or fixed effect models were employed to extract pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Our results indicated that high CD3+ lymphocyte infiltration in all the locations (AG), the tumor nest (TN), and the tumor stroma (TS) predicted better overall survival (OS) (HR=0.71, 95% CI=0.57-0.90; HR=0.58, 95% CI=0.42-0.80; and HR=0.50, 95% CI=0.37-0.68, respectively). CD8+ T cell infiltration in AG and FoxP3+ regulatory T cells (Tregs) in the tumor invasive margin (TM) were also associated with improved OS (HR=0.90, 95% CI=0.83-0.97; HR=0.65, 95% CI=0.48-0.87, respectively). However, contrasting results were found in the macrophage subset, with M2 in AG (HR=1.45, 95% CI=1.13-1.86) and the TN (HR=1.67, 95% CI=1.12-2.48) associated with worse OS. In summary, the combination of the densities and locations of tumor-infiltrating immune cells can be useful for predicting survival for GC patients, but additional research is needed to reinforce the reliability of this study’s conclusions.
Highlights
Gastric cancer (GC) is one of the most common malignancies
We found that a high density of tumor-infiltrating CD8+ lymphocytes counted in all locations (AG) was associated with good overall survival (OS) (HR=0.90, 95% confidence intervals (CIs)=0.83-0.97, I2=49.6%, P=0.114) but that OS was not correlated with specific infiltration locations, such as the tumor nest (TN) (HR=0.79, 95% CI=0.60-1.04; I2=28.1%,P=0.235), the tumor stroma (TS) (HR=1.39, 95% CI=0.92-2.08; I2=20.0%, P=0.264) or the tumor invasive margin (TM) (HR=0.75, 95% CI=0.52-1.09; I2=15.7%, P=0.276) (Figure 3A)
Tumor-infiltrating immune cells can influence the prognosis of cancer patients by directly or indirectly participating in immune responses and angiogenesis
Summary
Gastric cancer (GC) is one of the most common malignancies. Its incidence and mortality rates ranked fifth and second in 2013, respectively, placing a heavy burden on the public health system worldwide, especially in East Asian countries [1, 2]. Diagnosis and treatment strategies are based on the TNM staging system, which has been revised and perfected over the past 80 years. The prognosis of GC can be affected by several factors, such as tumor volume, patient age, and nutrition status. GC patients with the same TNM stage can have different clinical outcomes, causing unreliability in the TNM staging system for prognosis assessments. A new method to improve the accuracy of the TNM staging system is urgently needed
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