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. 2023 Aug 1;19(2):2232247.
doi: 10.1080/21645515.2023.2232247.

IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture

Chrystel Marton  1   2 , Alix Minaud  1 , Charles-Antoine Coupet  2 , Manon Chauvin  1 , Jamila Dhiab  1 , Hélène Vallet  1   3 , Jacques Boddaert  1   4 , Nadine Kehrer  2 , Bérangère Bastien  5 , Geneviève Inchauspe  2 , Luc Barraud  2 , Delphine Sauce  1
Affiliations

IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture

Chrystel Marton et al. Hum Vaccin Immunother. .

Abstract

Following acute stress such as trauma or sepsis, most of critically ill elderly patients become immunosuppressed and susceptible to secondary infections and enhanced mortality. We have developed a virus-based immunotherapy encoding human interleukin-7 (hIL-7) aiming at restoring both innate an adaptative immune homeostasis in these patients. We assessed the impact of this encoded hIL-7 on the ex vivo immune functions of T cells from PBMC of immunosenescent patients with or without hip fracture. T-cell ex vivo phenotyping was characterized in terms of senescence (CD57), IL-7 receptor (CD127) expression, and T cell differentiation profile. Then, post stimulation, activation status, and functionality (STAT5/STAT1 phosphorylation and T cell proliferation assays) were evaluated by flow cytometry. Our data show that T cells from both groups display immunosenescence features, express CD127 and are activated after stimulation by virotherapy-produced hIL-7-Fc. Interestingly, hip fracture patients exhibit a unique functional ability: An important T cell proliferation occurred compared to controls following stimulation with hIL-7-Fc. In addition, stimulation led to an increased naïve T cell as well as a decreased effector memory T cell proportions compared to controls. This preliminary study indicates that the produced hIL-7-Fc is well recognized by T cells and initiates IL-7 signaling through STAT5 and STAT1 phosphorylation. This signaling efficiently leads to T cell proliferation and activation and enables a T cell "rejuvenation." These results are in favor of the clinical development of the hIL-7-Fc expressing virotherapy to restore or induce immune T cell responses in immunosenescent hip fracture patients.

Keywords: Immunosenescence; T-cell functions; cytokine; hip fracture; immunosuppression; immunotherapy; interleukin-7; trauma; virotherapy.

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Conflict of interest statement

C Marton, CA Coupet, N Kehrer, B Bastien, L Barraud and G Inchauspé were employees of Transgene when the work was performed. Transgene SA is a publicly traded French biopharmaceutical company with Institut Merieux as major shareholder.

Figures

Figure 1.
Figure 1.
Ex vivo characterization of T cells in senescent patients with or without hip fracture.
Figure 2.
Figure 2.
Ex vivo characterization of IL-7 signaling induction by MVA-Hil-7-Fc supernatant treatment in CD8 and CD4 T cells from senescent patients with or without hip fracture.
Figure 3.
Figure 3.
Ex vivo characterization of CD8 and CD4 T cells activation after MVA-Hil-7-Fc supernatant treatment in senescent patients with or without hip fracture.
Figure 4.
Figure 4.
Immunophenotyping after 5 d of stimulation with MVA-hIL7-Fc supernatant.
Figure 5.
Figure 5.
T cell proliferation after 5 d of stimulation with MVA-hIL7-Fc supernatant.
See this image and copyright information in PMC

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