Abstract
Background: Tumor-infiltrating lymphocytes (TILs) play a role in the anti-tumor immune response, and are often found in esophageal squamous cell carcinoma (ESCC).Methods: We performed a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes of TILs based on their abundance and infiltrating location. A literature search of PubMed/Medline, Embase, Web of Science and the Cochrane Library was conducted. Studies that investigated the prognostic significance of generalized, CD8+, CD4+, FoxP3+, CD3+, and CD45O+ TILs in ESCC patients were included.Results: In pooled analysis, generalized TILs infiltrating the entire tumor mass were positively associated with disease-free survival (DFS), with a univariate-related hazard ratio (HR) of 0.630 [95% confidence interval (CI) 0.415–0.955], and also positively associated with overall survival (OS), with a univariate-related HR of 0.586 (0.447–0.770) and a multivariate-related HR of 0.621 (0.439–0.878). The pan-tumor, intra-tumor and peri-tumor CD8+ TILs had a favorable effect on OS, with univariate-related HRs of 0.733 (0.555–0.968), 0.797 (0.660–0.962), and 0.776 (0.635–0.948), respectively. Similar results were observed in CD8+ TILs that infiltrated the whole tumor mass, with a multivariate-related HR of 0.705 (0.524–0.947). CD4+, FoxP3+, CD3+, and CD45O+ TILs were not linked to DFS or OS. Subtypes and spatial locations of TILs seemed to influence study outcomes.Conclusions: Experimental and analytical methods of future studies should be carefully designed to avoid overestimating the effect of TILs on prognosis. Our meta-analysis confirms the prognostic efficacy of generalized TILs and CD8+ TILs in esophageal squamous cell carcinoma (ESCC) patients.
Highlights
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies [1]
One study comes from a non-Asian country [13], which is consistent with the fact that Asians are susceptible to esophageal squamous cell carcinoma (ESCC) due to their hereditary backgrounds [32]
In this systematic review and meta-analysis, almost no study presented detailed information about participants who were lost during follow-up, and most studies did not report any reasons for non-completion
Summary
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies [1]. The 5-year survival rate is ∼20%, largely due to late diagnosis and propensity for metastasis. Some studies indicated the presence of tumor-infiltrating lymphocytes (TILs) to be a favorable prognostic factor for survival in ESCC patients [4,5,6]. Patients with abundant infiltration of CD4+ T helper type 1 lymphocytes (Th1) showed improved survival rates by stimulating CTLs, while CD4+ regulatory T cells (Tregs) are thought to inhibit effective antitumor response [12]. Several studies have investigated the prognostic value of TILs based on their infiltrating location To this end, we evaluated the prognostic efficacy of the different TIL subsets in ESCC, and determined the effect of their anatomical location. Tumor-infiltrating lymphocytes (TILs) play a role in the anti-tumor immune response, and are often found in esophageal squamous cell carcinoma (ESCC)
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