American Association for Cancer Research
10780432ccr201420-sup-241363_2_supp_6476822_q8lh8c.pdf (57.09 kB)

Figure S3 from 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

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posted on 2023-03-31, 22:27 authored by Roberto Ferrara, Marie Naigeon, Edouard Auclin, Boris Duchemann, Lydie Cassard, Jean-Mehdi Jouniaux, Lisa Boselli, Jonathan Grivel, Aude Desnoyer, Laura Mezquita, Matthieu Texier, Caroline Caramella, Lizza Hendriks, David Planchard, Jordi Remon, Sabina Sangaletti, Claudia Proto, Marina C. Garassino, Jean-Charles Soria, Aurelien Marabelle, Anne-Laure Voisin, Siham Farhane, Benjamin Besse, Nathalie Chaput

Comparison of progression free survival and overall survival between the discovery and validation cohorts



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. 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. 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. 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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