TCF1+PD-1+ tumour-infiltrating lymphocytes predict a favorable response and prolonged survival after immune checkpoint inhibitor therapy for non-small-cell lung cancer

Jaemoon Koh, Sehui Kim, Yeon Duk Woo, Seung Geun Song, Jeemin Yim, Bogyeong Han, Sojung Lim, Hyun Kyung Ahn, Seungchan Mun, Jung Sun Kim, Bhumsuk Keam, Young A. Kim, Se Hoon Lee, Yoon Kyung Jeon, Doo Hyun Chung

Research output: Contribution to journalArticlepeer-review

Abstract

Background: T-cell factor 1 (TCF1)+Programmed cell death-1 (PD-1)+ tumour-infiltrating lymphocytes (TILs) are a recently defined subset of exhausted T-cells (Texh-cells) that exhibit a progenitor phenotype. They have been associated with a response to immune checkpoint inhibitor (ICI) therapy in murine tumour models and in patients with malignant melanoma. We investigated the significance of TCF1+PD-1+ TILs as a predictive biomarker for ICI therapy response in non-small-cell lung cancer (NSCLC). Methods: Two different cohorts of NSCLC patients treated with ICI targeting the PD-1/PD-L1 pathway were included. RNA-seq was performed using NSCLC tissues obtained from 234 patients prior to immunotherapy (RNA-seq cohort). Double immunostaining of TCF1 and PD-1 and single immunostaining of other immunologic markers were performed in resected tumour tissues from another 116 patients (immunohistochemistry cohort). Results: In the RNA-seq cohort, both Texh-cell and progenitor Texh-cell gene sets were enriched in responders compared with non-responders. Larger Texh-cell fractions and increased progenitor Texh-cell gene sets were significantly associated with better progression-free survival (PFS). In the immunohistochemistry cohort, the TCF1+PD-1+ TIL number and PD-L1 tumour proportion score were significantly higher in responders than in non-responders. A high number of TCF1+PD-1+ TILs was significantly associated with both PFS and overall survival (OS) after ICI therapy, and it independently predicted a better PFS and OS according to multivariate analysis. Conclusion: TCF1+PD-1+ TILs, representing progenitor Texh-cells, predict both better response and survival in NSCLC patients after ICI therapy. Thus, they may be a useful predictive biomarker for ICI therapy in NSCLC.

Original languageEnglish
Pages (from-to)10-20
Number of pages11
JournalEuropean Journal of Cancer
Volume174
DOIs
StatePublished - Oct 2022

Keywords

  • Exhausted T cells
  • Immune checkpoint inhibitor
  • Immunotherapy
  • Non-small cell lung cancer
  • PD-1
  • Precursor exhausted T cells
  • Predictive biomarker
  • TCF1
  • Tumor microenvironment

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