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Comment
. 2021 Jan 15;27(2):492-503.
doi: 10.1158/1078-0432.CCR-20-1420. Epub 2020 Sep 4.

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

Roberto Ferrara #  1   2   3   4 , Marie Naigeon #  1   5 , Edouard Auclin  6 , Boris Duchemann  1 , Lydie Cassard  1 , Jean-Mehdi Jouniaux  1 , Lisa Boselli  1 , Jonathan Grivel  1 , Aude Desnoyer  1 , Laura Mezquita  2 , Matthieu Texier  7 , Caroline Caramella  8 , Lizza Hendriks  2   9 , David Planchard  2 , Jordi Remon  2 , Sabina Sangaletti  4 , Claudia Proto  3 , Marina C Garassino  3 , Jean-Charles Soria  5 , Aurelien Marabelle  10 , Anne-Laure Voisin  11 , Siham Farhane  11 , Benjamin Besse #  12   5 , Nathalie Chaput #  13   14
Affiliations
Comment

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

Roberto Ferrara et al. Clin Cancer Res. .

Abstract

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 cut-off 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 TNFα and IFNγ 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.See related commentary by Salas-Benito et al., p. 374.

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References

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