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10780432ccr201420-sup-241363_2_supp_6476824_q7lh7c.pdf (53.64 kB)

Figure S5 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

Optimization of SIP cut-off according to maximization of log-likelihood ratio method (A). Variation of HR for PFS (blue line) according to circulating senescent lymphocytes (% CD28- CD57+ KLRG1+ among CD8+ T-cells) (B) (ICI discovery cohort)

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ARTICLE ABSTRACT

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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