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Updated: Aug 18, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Tumor Infiltrating Lymphocyte Expression of PD-1 Predicts Response to Anti-PD-1/PD-L1 Immunotherapy
Nicholas J Bevins1, Ryosuke Okamura2, Meagan Montesion3
1Department of Pathology, University of California San Diego, San Diego, CA USA.
Introduction:
Many studies have focused on the role of programmed death receptor ligand 1 (PD-L1) expression in predicting immunotherapy outcomes. Limited clinical data are available regarding the role of programmed death receptor 1 (PD-1; the PD-L1 receptor) expressing tumor-infiltrating lymphocytes (TILs) in PD-1/PD-L1 antibody responsiveness. However, preclinical studies demonstrate that TILs expressing PD-1 contribute to tumor immune evasion.
Methods:
This study analyzed the association between TIL-PD-1 status and outcome after immune checkpoint blockade (ICB) therapy. We evaluated 123 patients with various solid tumors treated with monoclonal antibodies targeting the PD-1/PD-L1 signaling axis. Additionally, 8706 solid tumor specimens were assessed for TIL-PD-1 and tumor mutational burden (TMB) status.
Results:
The presence of PD-1-expressing TILs in tumors was associated with increased median progression-free survival (7.0 vs 1.9 months; p = 0.006) and overall survival (18.1 vs 8.0 months; p = 0.04) after treatment with ICB. TIL-PD-1-positive patients had an objective response rate (ORR) of 41% (95% CI, 24-61; N = 12/29) compared with 17% (95% CI, 4-43; N = 3/17) for TIL-PD-1-negative patients (p = 0.18). Analyzed as continuous variables, TIL-PD-1 and TMB showed a weak correlation in 8706 solid tumor samples (Pearson r = 0.074); when analyzed as categorical variables (cutoffs: TIL-PD-1 ≥ 1% and TMB ≥ 10 mutations/Mb), the two variables are correlated (p < 0.0001). TIL-PD-1-positive status is also associated with enrichment of pathologic variants within several genes, most notably TP53 (adjusted p < 0.05).
Conclusion:
TIL-PD-1 positivity in tumors (≥ 1%) is associated with significantly longer progression-free and overall survival after ICB. ClinicalTrials.gov ID: NCT02478931.
