Clinical and Prognostic Significance of Tumor-Infiltrating CD8+ T Cells and PD-L1 Expression in Primary Gastrointestinal Stromal Tumors

Abstract

PurposeImmunotherapy for gastrointestinal stromal tumors (GISTs) remains a clinical challenge. The present study aimed to explore the clinical and prognostic significance of immune cell infiltration and PD-L1 expression in GISTs.MethodsA total of 507 clinical tissue specimens of primary GISTs were collected for immunohistochemical analysis of immune cell infiltration and PD-L1 expression. Influencing factors of survival were evaluated by Kaplan–Meier analysis. Univariate and multivariate analyses were performed using the Cox regression model.ResultsThere were significant differences in sex, tumor location, size, mitotic index, NIH risk grade, and cell morphology between different gene mutation types of GISTs. Immune cell infiltration in GISTs mainly involved macrophages and T cells. PD-1 was expressed in 48.5% of the tissue specimens, and PD-L1 expression was detected in 46.0% of the samples. PD-L1 expression was negatively correlated with the tumor size and mitotic index but positively correlated with the number of CD8+ T cells. There were significant differences in the number of CD8+ T cells between different gene mutation types. Wild type-mutant GISTs were enriched with CD8+ T cells as compared with KIT- and PDGFRA-mutant GISTs. The number of CD8+ T cells was higher in non-gastric GISTs. PD-L1 and CD8+ T cells were independent predictors for better relapse-free survival of GISTs.ConclusionsPD-L1 expression is a predictive biomarker for better prognosis of GISTs. Non-gastric GIST patients with wild-type mutations may be the beneficiaries of PD-1/PD-L1 inhibitors.

Construction and validation of a prognostic model for gastrointestinal stromal tumors based on copy number alterations and clinicopathological characteristics

“…As next-generation sequencing technology continues to evolve, an increasing number of genomic-based prognostic models are being developed ( 17 , 18 ). Wei’s team incorporated immune infiltration indicators and PD-L1 to build a prognostic model for patients with GISTs through the lasso-Cox model.…”

Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers

“…Moreover, there are also some less abundant immune cells infiltrated in GIST, including natural killer (NK) cells, B lymphocytes, dendritic cells (DCs), natural killer T (NKT) cells, gamma delta (γδ) T cells, neutrophils, eosinophils and mast cells, etc. [ 42 , 94 , 96 , 100 , 101 , 103 , 106 , 113 – 115 ]. The intratumoral distribution patterns of immune cells in GIST are variable; they are mainly diffusely distributed around blood vessels with a small amount distributed in aggregates [ 94 , 96 , 100 , 101 , 105 ].…”

Prognostic and clinicopathological significance of the Prognostic Nutritional Index in patients with gastrointestinal stromal tumours undergoing surgery: a meta-analysis

“…35 A novel nomogram based on sarcopenia was established to predict the OS of patients with GISTs. 35 Programmed cell death-ligand 1 expression is a predictive biomarker for better prognosis of GISTs, 36 and the number of tumour-infiltrating CD8+T cells is higher in non-gastric GISTs. 36 Moreover, the OS of GIST patients with gastrointestinal bleeding was worse than non-GI bleeding, but had no significant effect on RFS.…”

“…35 Programmed cell death-ligand 1 expression is a predictive biomarker for better prognosis of GISTs, 36 and the number of tumour-infiltrating CD8+T cells is higher in non-gastric GISTs. 36 Moreover, the OS of GIST patients with gastrointestinal bleeding was worse than non-GI bleeding, but had no significant effect on RFS. 37 In addition to patients with cancer, there is evidence suggesting that the PNI may be used to predict outcomes in patients with infections, such as COVID-19.…”