Low CD8⁺ T Cell Infiltration and High PD-L1 Expression Are Associated with CD44⁺/CD133⁺ Cancer Stem Cells and Predict an Unfavorable Prognosis in Pancreatic Cancer

Abstract

Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effect to evade the immune recognition. However, clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC. Immunostaining and quantitative analysis were performed to assess CD8+ T cells infiltration, PD-L1 expression, and their relationship with CD44+/CD133+ CSCs and disease progression in PC. CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression group show high levels of CD44+/CD133+ CSCs, but patients with low CD8+ T cells infiltration/high PD-L1 expression had worse survival and higher recurrence risk than those with high CD8+ T cells infiltration/high PD-L1 expression. Moreover, CD8+ T cells infiltration could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/CD133. Our study highlights an interaction among CD8+ T cells infiltration, PD-L1 expression, and CD44+/CD133+ CSCs existence, which contributes to PC progression and immune evasion.

Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer

“…Although T cell subsets play an important role in tumor inhibition, some T cell types promote tumor progression through different growth factors [50]. For example, the presence of CD8 + and CD4 + T cells could improve clinical outcomes and prolong survival in different cancers [51][52][53][54], while T cell regulation (Tregs) may inhibit antitumor immune response and support the establishment of immune hyporesponse microenvironments in some tumor types [55]. Macrophages, an important component of TIICs, serve as the key mediator between inflammation and cancer [56,57].…”