Circulating T-cell Immunosenescence in Patients with Advanced Non-small Cell Lung Cancer Treated with Single-agent PD-1/PD-L1 Inhibitors or Platinum-based Chemotherapy

R. Ferrara, M. Naigeon, E. Auclin, B. Duchemann, L. Cassard, J.M. Jouniaux, L. Boselli, J. Grivel, A. Desnoyer, L. Mezquita, M. Texier, C. Caramella, L. Hendriks, D. Planchard, J. Remon, S. Sangaletti, C. Proto, M.C. Garassino, J.C. Soria, A. MarabelleA.L. Voisin, S. Farhane, B. Besse*, N. Chaput*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Purpose: CD28, CD57, and KLRG1 have been previously identified as markers of T-cell immunosenescence. The impact of immunosenescence on anti-PD(L)-1 (ICI) or platinum-based chemotherapy (PCT) in patients with advanced non-small cell lung cancer (aNSCLC) is unknown.Experimental Design: The percentage of CD28(-), CD57(+), KLRG1(+) among CD8(+) T cells [senescent immune phenotype (SIP)] was assessed by flow cytometry on blood from patients with aNSCLC before single-agent ICI (discovery cohort). A SIP cutoff was identified by log-rank maximization method and patients with aNSCLC treated with ICI (validation cohort) or PCT were classified accordingly. Proliferation and functional properties of SIP+ CD8(+) T cells were assessed in vitro.Results: In the ICI discovery cohort (N = 37), SIP cut-off was 39.5%, 27% of patients were SIP+. In the ICI validation cohort (N = 46), SIP+ status was found in 28% of patients and significantly correlated with worse objective response rate (ORR; 0% vs. 30%, P = 0.04), median progression-free survival (PFS) [1.8 (95% confidence interval (CI), 1.3-NR) vs. 6.4 (95% CI, 2-19) months, P = 0.009] and median overall survival, OS [2.8 (95% CI, 2.0-NR) vs. 20.8 (95% CI, 6.0-NR) months, P = 0.02]. SIP+ status was significantly associated with circulating specific immunephenotypes, in vitro lower CD8(+) T cells proliferation, lower IL2 and higher TNF alpha and IFN gamma production. In the ICI-pooled population (N = 83), SIP+ status did not correlate with any clinical characteristics and it was associated with significantly worse ORR, PFS, and OS. In PCT cohort (N = 61), 11% of patients were SIP+. SIP status did not correlate with outcomes upon PCT.Conclusions: Circulating T-cell immunosenescence is observed in up to 28% of patients with aNSCLC and correlates with lack of benefit from ICI but not from PCT.
Original languageEnglish
Pages (from-to)492-503
Number of pages12
JournalClinical Cancer Research
Issue number2
Publication statusPublished - 15 Jan 2021


  • biomarkers
  • blockade
  • docetaxel
  • elderly-patients
  • nivolumab
  • nsclc
  • outcomes
  • pd-1
  • replicative senescence
  • therapy
  • PD-1

Cite this