ImmunoTargets and therapy · 2026
Prognostic and Predictive Value of Peripheral CD8/PD-1/TCF-1 Positive T Cells in Non-Small Cell Lung Carcinoma Patients.
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Xagara Anastasia, Goulielmaki Maria, Chantzara Evangelia, Koinis Filippos, Fortis Sotiris P, Hatzidaki Dora, Ntostoglou Konstantinos, Christodoulopoulos George, Saloustros Emmanouil, Karagiannis Sophia N, Frisan Teresa, Baxevanis Constantin N, Georgoulias Vassilis, Pateras Ioannis S, Kotsakis Athanasios
Аннотация
INTRODUCTION: Novel predictive biomarkers are needed to optimize immunotherapy-based treatment response in non-small cell lung carcinoma (NSCLC). T cell modulatory features may limit the ability of T cells to mount effective anti-tumor responses and could predict immune fitness and responsiveness to therapy. We investigated the prognostic and predictive value of CD8+ T cells with an exhausted phenotype, specifically those co-expressing Programmed Death 1 (PD-1) and T cell factor 1 (TCF-1), in peripheral blood of NSCLC patients before any systemic treatment.
METHODS: Two patient cohorts were analyzed: a) 32 patients with early and locally advanced disease (stage I-IIIA; cohort A) who did not receive immunotherapy, and b) 47 patients with advanced disease (stage IIIB-IV) who received chemo-immunotherapy. Multicolor flow cytometry was used to assess CD8+ T cell subpopulations co-expressing PD-1 and TCF-1.
RESULTS: PD-1+TCF1+ progenitor (early) exhausted T cells were found at high frequencies in all NSCLC patients compared with healthy donors, regardless of tumor stage. In cohort A, patients with high levels of CD3+CD8+PD-1+TCF1+ T cells had significantly improved DFS (p= 0.038), while those with high CD3+CD8+PD-1+TCF1- T cells had significantly worse DFS (p= 0.028). In cohort B, high levels of CD3+CD8+PD-1+TCF1+ T cells were associated with shorter PFS (p= 0.027). No association with OS was observed in cohort A. Conversely, in cohort B, high CD3+CD8+PD-1+TCF1+ T cell levels correlated with shorter OS (p= 0.045), while high CD3+CD8+PD-1+TCF1- T cell levels correlated with longer OS (p= 0.010).
CONCLUSION: Therefore, here we show that circulating PD-1⁺TCF1+ T cells correlated differentially with treatment outcome in early and late NSCLC stage patients.
METHODS: Two patient cohorts were analyzed: a) 32 patients with early and locally advanced disease (stage I-IIIA; cohort A) who did not receive immunotherapy, and b) 47 patients with advanced disease (stage IIIB-IV) who received chemo-immunotherapy. Multicolor flow cytometry was used to assess CD8+ T cell subpopulations co-expressing PD-1 and TCF-1.
RESULTS: PD-1+TCF1+ progenitor (early) exhausted T cells were found at high frequencies in all NSCLC patients compared with healthy donors, regardless of tumor stage. In cohort A, patients with high levels of CD3+CD8+PD-1+TCF1+ T cells had significantly improved DFS (p= 0.038), while those with high CD3+CD8+PD-1+TCF1- T cells had significantly worse DFS (p= 0.028). In cohort B, high levels of CD3+CD8+PD-1+TCF1+ T cells were associated with shorter PFS (p= 0.027). No association with OS was observed in cohort A. Conversely, in cohort B, high CD3+CD8+PD-1+TCF1+ T cell levels correlated with shorter OS (p= 0.045), while high CD3+CD8+PD-1+TCF1- T cell levels correlated with longer OS (p= 0.010).
CONCLUSION: Therefore, here we show that circulating PD-1⁺TCF1+ T cells correlated differentially with treatment outcome in early and late NSCLC stage patients.