The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age

E Orillard; L Spehner; L Mansi; A Bouard; A Falcoz; Q Lepiller; E Renaude; J R Pallandre; A Vienot; M Kroemer; C Borg

doi:10.3389/fimmu.2023.1160664

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age

Front Immunol. 2023 Jun 2:14:1160664. doi: 10.3389/fimmu.2023.1160664. eCollection 2023.

Authors

E Orillard^{1

2}, L Spehner^{1

2}, L Mansi^{1

2}, A Bouard³, A Falcoz^{2

4}, Q Lepiller^{5

6}, E Renaude², J R Pallandre^{2

3}, A Vienot^{1

2}, M Kroemer^{2

3

7}, C Borg^{1

2

3}

Affiliations

¹ Department of Oncology, University Hospital of Besançon, Besançon, France.
² Bourgogne Franche-Comté University, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie cellulaire et Génique, Besançon, France.
³ ITAC Platform, University of Bourgogne Franche-Comté, Besançon, France.
⁴ Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, Besançon, France.
⁵ Department of Virology, University Hospital of Besançon, Besançon, France.
⁶ Research Unit EA3181, Université de Franche Comté, Besançon, France.
⁷ Department of Pharmacy, University Hospital of Besançon, Besançon, France.

Abstract

Purpose: Cancer patients are at risk of severe COVID-19 infection, and vaccination is recommended. Nevertheless, we observe a failure of COVID-19 vaccines in this vulnerable population. We hypothesize that senescent peripheral T-cells alter COVID-19 vaccine-induced immunity.

Methods: We performed a monocentric prospective study and enrolled cancer patients and healthy donors before the COVID-19 vaccination. The primary objective was to assess the association of peripheral senescent T-cells (CD28^-CD57⁺KLRG1⁺) with COVID-19 vaccine-induced immunity.

Results: Eighty cancer patients have been included, with serological and specific T-cell responses evaluated before and at 3 months post-vaccination. Age ≥ 70 years was the principal clinical factor negatively influencing the serological (p=0.035) and specific SARS-CoV-2 T-cell responses (p=0.047). The presence of senescent T-cells was correlated to lower serological (p=0.049) and specific T-cell responses (p=0.009). Our results sustained the definition of a specific cut-off for senescence immune phenotype (SIP) (≥ 5% of CD4 and ≥ 39.5% of CD8 T-cells), which was correlated to a lower serological response induced by COVID-19 vaccination for CD4 and CD8 SIP^high (p=0.039 and p=0.049 respectively). While CD4 SIP level had no impact on COVID-19 vaccine efficacy in elderly patients, our results unraveled a possible predictive role for CD4 SIP^high T-cell levels in younger cancer patients.

Conclusions: Elderly cancer patients have a poor serological response to vaccination; specific strategies are needed in this population. Also, the presence of a CD4 SIP^high affects the serological response in younger patients and seems to be a potential biomarker of no vaccinal response.

Keywords: COVID-19, vaccination; T lymphocyte (T-cell); cancer patient; predictive biomarker; senescence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 Vaccines
COVID-19* / prevention & control
Humans
Neoplasms*
Prospective Studies
SARS-CoV-2

Substances

COVID-19 Vaccines

Grants and funding

This work was supported by a grant from the Foundation ARC to Laura Mansi (CANCER EMERGENCY & COVID-19, December 2020) and from the regional Health agency Bourgogne Franche-Comté (ARS BFC) to Christophe Borg (Evaluation of efficacy and predictors of response to COVID-19 vaccine in cancer patients in hospitals of Regional Institute of Franche-Comté (IRFC), January 2021). The sponsors had no role in the study design, data collection, and analysis, in the preparation of the manuscript, or in the decision to publish.