Abstract 5937
Background
iSenescence is a progressive remodeling of immune functions with a multifactorial etiology (i.e. aging, chronic inflammation, cancer). Although the absence of CD28 and the expression of CD57 and Killer-cell lectin-like receptor G1 (KLRG1) on peripheral T-lymphocytes are potential hallmarks of iSenescence, the characterization of such phenotype in IO-treated aNSCLC patients and the correlation with clinical characteristics and benefit from immunotherapy are currently unknown.
Methods
A senescent immune phenotype (SIP) defined as a percentage of circulating CD8+CD28-CD57+KLRG1+ T-lymphocytes was assessed by flow cytometry (FC) on fresh blood from aNSCLC patients treated with IO in a single institution (03/2017–04/2018). A log-rank maximization method was used to identify a SIP cut-off level and dichotomize patients accordingly. The objective was to correlate SIP with clinical characteristics and RECIST response by univariate logistic regression analysis.
Results
39 aNSCLC patients were evaluable for SIP before IO: 38% ≥ 65 years, 87% non-squamous, 38% KRAS mutated, 54% with PD-L1 expression ≥1%, 13% chemotherapy naïve. Among 30 patients evaluable for IO response, 53% had progression (PD), 27% stability (SD), 20% partial response (PR). Median PFS was 1.9 months (95% CI 1.5; 2.5). OS was not calculated due to the short follow-up [6 months (95% CI 4-11)]. SIP (% CD28-CD57+KLRG1+) median value on circulating CD8+ lymphocytes was 15.26% (min 1.87%, max 56.28%). Overall, 13 (33%) of 39 patients had >22.25% CD8+ lymphocytes with a CD28-CD57+KLRG1+ phenotype, being classified as SIP+. SIP status did not significantly correlate with age, IO-baseline patients’ characteristics or previous chemotherapy exposure. Among patients evaluable for IO response, only 1 (10%) of 10 SIP+ experienced disease control (PR/SD), compared to 13 (65%) of 20 SIP- patients; similarly, PD rate was significantly higher in SIP+ compared to SIP- patients (90% vs 35%, p = 0.007).
Conclusions
iSenescence, monitored by FC measurement of 3 surface molecules on circulating CD8 + lymphocytes, is observed in 33% of aNSCLC patients, is independent of age and correlates with lower disease control rate upon IO.
Clinical trial identification
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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