Poster Display Poster Display session

20P - Human virome epitope-level antiviral antibody profiling identified the cytomegalovirus (CMV) as the main driver of Senescent Immune Phenotype (SIP) in patients with advanced non-small cell lung cancer patients (aNSCLC) (ID 121)

Presentation Number
20P
Lecture Time
12:30 - 12:30
Speakers
  • Marie Naigeon (Villejuif, Cedex, France)
Session Name
Poster Display
Room
Foyer mezzanine
Date
Thu, Dec 8, 2022
Time
12:30 - 13:15

Abstract

Background

Immunosenescence is a progressive remodeling of immune functions with a multifactorial etiology including aging and chronic antigenic stressors (inflammation, infections, cancer). We showed that a high pretreatment SIP (CD28–CD57+KLRG1+CD8+ circulating T cells>39.5%, SIP+) was associated with resistance to ICB in patients with aNSCLC. Chronic viral infections may speed up immune aging, especially CMV which affects blood T cells phenotype (loss of CD28, overexpression of CD57). We aimed to assess antiviral serological profile and its association with SIP status.

Methods

Baseline SIP status was assessed by flow cytometry on fresh blood samples from ICB-treated and polychemotherapy-treated (PCT) aNSCLC patients. Sera from patients were analysed with VirScan (CDI Labs, USA), a high-throughput antiviral antibody (Ab) method (VirScan™) enabling simultaneous epitope-level antiviral antibody profiling of most viruses with human tropism (206 species, 1000 strains) via phage-display and immunoprecipitation sequencing (PhIP-Seq).

Results

132 aNSCLC patients were evaluable for SIP and VirScan™ assay. The antiviral serological profile seems similar between SIP+ and SIP- patients, except for CMV where the mean enrichment of anti-CMV antibodies was higher in SIP+. Of the 74 antiviral Ab associated with a higher SIP, 70 (94.6%) recognized CMV-peptides and CMV was the only virus globally associated with a higher SIP. SIP+ patients were predominantly CMV+ compared to SIP- (93% vs 57%, p<0.001), but 70.5% of CMV+ remained SIP-. In CMV+ patients, no difference was observed in the number of CMV epitodes targeted by antibodies (p=0.62) nor in protein immunisation profile between SIP+ and SIP- patients. Among all clinic-biological parameters studied only median age was higher in SIP+ (71 years vs 63 years, p=0.01) compared to SIP- in CMV+ patients.

Conclusions

Among 206 species, only anti-CMV Ab were associated with SIP+ status, which is associated with an older age in CMV+ patients. Further work investigating the predictive value of CMV in the response to ICB in older patients is ongoing.

Clinical trial identification

NCT03984318, NCT02105168.

Legal entity responsible for the study

Gustave Roussy.

Funding

ANR-21-RHUS-0013, Malakoff Médéric.

Disclosure

All authors have declared no conflicts of interest.

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