Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a meta-analysis and experimental validation

Abstract

Introduction: We performed a meta-analysis and an experimental validation to investigate the association between tumor infiltrating lymphocytes (TILs) and the outcome of gastric cancer (GC) patients to provide prognostic indicators for clinical practice. Material and methods: The relative literature of TILs in tumor tissue from patients with gastric cancer was searched from PubMed, Embase, NIH databases, from April 2000 to 31 December 2016. Studies on the prognostic value of TILs as CD3+, CD4+, CD8+, GrB+, and FOXP3+ lymphocytes for GC were retrieved, and also the related references were traced as supplements. Independent screening documents, extracting information and evaluating quality were implemented independently by 2 evaluators according to the inclusion and exclusion criteria, which were then analyzed by meta-analysis using STATA version 12.0 software. Results: The results indicated that high levels of intratumoral CD8+, CD3+ and CD4+ T cell infiltration were associated with better overall survival(OS) in gastric cancer patients, while high density of intratumoral FOXP3+ T cells was not closely associated with a worse outcome. Additionally, in our study, higher density of granzyme B+ (GrB+) T cell infiltration indicated an optimistic prognosis, and infiltration of a larger number of general TILs also suggested a favorable prognosis by log-rank test analysis. Conclusions: This meta-analysis clarified that high levels of CD8+, CD3+, and CD4+ T cell infiltration in tumor tissue showed better OS in GC patients, whereas high density of FOXP3+ T cell infiltration may not be recognized as a negative prognostic factor. These results may provide some useful prognostic indicators for clinical application in gastric cancer.

Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density

“…Most studies of TILs (including CD8+ T cells) and B7-H3 in GC are carried out on Asian cohorts. According to their meta-analyses, higher intratumour CD8 expression is associated with an improved overall survival [ 2 , 12 ]. Distinct tumour immunity signatures between Asian and non-Asian GCs have been found, including higher expression of CD8 in Western GCs [ 13 ].…”

“…They are able to recognize tumour-specific antigens and destroy cancer cells by perforin and granzyme-mediated apoptosis. Studies show that a higher amount of CD8+ T cells in the tumour is associated with better prognosis in gastric cancer (GC) [ 2 , 3 ]. However, during cancer progression they become inactivated due to the immunosuppressive nature of TIME.…”

Locally advanced gastroesophageal junction cancer with pathological complete response to neoadjuvant therapy: a case report and literature review

“…According to previous studies, chemotherapy leads to the death of tumor cells, which may increase antigen presentation (62,78), while other research has found that neoadjuvant chemotherapy (NACT) also induces upregulated levels of CD8+, PD-1, and PD-L1 (79,80). In addition, CD45RO-positive T cells seem to express more interferon-γ (IFN-γ), and IFN-γ are likely to induce local immune activation (81) and the absence of immunosuppressive elements like FOXP3+ T cells (82). In our case, neoadjuvant chemotherapy may alter the tumor microenvironment, so that the patient could benefit from immunotherapy and achieved pCR.…”

Prediction of overall survival and response to immune checkpoint inhibitors: An immune-related signature for gastric cancer

“…The abundance of CD4 T cells, macrophage M2 and monocyte were high in the high-risk group, which seemed to be an explanation for the prognostic power of the signature. It is known that CD4+ T cells are essential organizers of cell-mediated immunity, participating in every stage of the immune response [ 20 ]. Naive CD4+ T cells can be induced to differentiate to specific lineages according to the local cytokine milieu, towards Th1, Th2, Th17 and Treg and Th17 cells with both anti-tumor and pro-tumor functions in different cancers [ 20 ].…”