Abstract
BackgroundTumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear. This study aimed to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs).MethodsUsing a prospective database containing 401 cases of GC, we evaluated TIL (cluster of differentiation 8 (CD8) expression) and TAM (cluster of differentiation 68 (CD68) expression) statuses via immunohistochemical staining.ResultsCompared with CD8+ TIL-negative cases (n = 196, 48.6%), CD8+ TIL-positive cases (n = 205, 51.1%) showed significantly better recurrence-free survival (RFS) [log-rank p<0.001; multivariate HR: 0.372; 95% confidence interval (CI): 0.239–0.579, p<0.001]. In contrast, compared with CD68+ TAM-negative cases (n = 217, 54.1%), CD68+ TAM-positive cases (n = 184, 45.9%) had significantly poor RFS [log-rank p<0.001; multivariate HR: 2.182; 95% CI: 1.435–3.318, p<0.001]. Thus, patients with a positive CD8+ TIL and negative CD68+ TAM status exhibited significantly increased RFS. Multivariate analysis demonstrated that CD8+ TILs and CD68+ TAMs may serve as independent prognostic markers for RFS. Incorporating CD8+ TIL and CD68+ TAM statuses into the AJCC TNM system generated a predictive model with better predictive accuracy for RFS. More importantly, patients with a positive TIL and negative TAM status showed a tendency of improved RFS after postoperative adjuvant chemotherapy (PAC). Similar results were obtained by overall survival (OS) analysis.ConclusionsCD8+ TIL and CD68+ TAM statuses were identified as independent prognostic factors that may be integrated into the current TNM staging system to refine risk stratification and to better predict the survival benefit from PAC in patients with GC.Trial registrationThe current controlled trial was registered at ClinicalTrials.gov (ID: NCT02327481) on December 30, 2014.
Highlights
Tumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear
In recent decades, convincing evidence has emerged that the tumor microenvironment (TME) and inflammation play a key role in the development of many malignant tumors, including GC [1, 9, 10]
The results indicate that the constructed model is advantageous with a higher threshold probability and improved performance for predicting 3-year recurrence-free survival (RFS) and 3-year overall survival (OS) than the TNM stage or Cluster of differentiation 8 (CD8)+ Tumor-infiltrating lymphocytes (TIL)/Cluster of differentiation 68 (CD68)+ Tumor-associated macrophages (TAM) status alone (Additional file 3: Figure S3)
Summary
Tumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear. This study aimed to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). There is considerable interest in exploring the potential benefits of PAC for GC patients. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) are two main components of the TME that have shown prognostic value in previous studies [11, 12]. Incorporating these immunological parameters into the established TNM staging system may increase the prognostic value for further stratification and better management of patients with different prognoses
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