Immune Profiling Uncovers Memory T-Cell Responses with a Th17 Signature in Cancer Patients with Previous SARS-CoV-2 Infection Followed by mRNA Vaccination

  1. Miriam Echaide
  2. Ibone Labiano
  3. Marina Delgado
  4. Angela Fernández de Lascoiti
  5. Patricia Ochoa
  6. Maider Garnica
  7. Pablo Ramos
  8. Luisa Chocarro
  9. Leticia Fernández
  10. Hugo Arasanz
  11. Ana Bocanegra
  12. Ester Blanco
  13. Sergio Piñeiro-Hermida
  14. Pilar Morente
  15. Ruth Vera
  16. Maria Alsina
  17. David Escors
  18. Grazyna Kochan

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Abstract

It is unclear whether patients with cancer present inherently impaired responses to COVID-19 and vaccination due to their treatments, neoplastic diseases or both. To address this question, immune profiling was performed in three cohorts of healthy donors and oncologic patients: infected with SARS-CoV-2, BNT162b2-vaccinated, and with previous COVID-19 disease and subsequently vaccinated. Cancer patients showed good antibody responses to vaccination, but poor induction of T-cell responses towards the S protein when compared to infection. Following natural infection, the major targets for T-cells were the SARS-CoV-2 structural proteins M and S, but not the N protein. Similar to antibody titers, the T-cell responses quickly decayed after six months post-vaccination. Significant memory T-cell expansion was observed in vaccinated donors only if previously diagnosed with COVID-19 before undergoing vaccination. Oncologic patients with previous COVID-19 followed by vaccination exhibited potent IL-17+ CD4 and CD8 T-cell responses and elevated numbers of circulating neutrophils in peripheral blood.

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  1. Version published to 10.3390/cancers14184464
  2. Version published to 10.1101/2022.05.27.22275672v2 on medRxiv
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    SciScore for 10.1101/2022.05.27.22275672: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The study was approved by the Clinical Research Ethics Committees of Hospital Universitario de Navarra and informed consents were obtained for all subjects.
    Consent: The study was approved by the Clinical Research Ethics Committees of Hospital Universitario de Navarra and informed consents were obtained for all subjects.
    Field Sample Permit: Infected patients were classified for COVID-19 severity according to the Treatment Guidelines of the NIH (https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/): Sample processing, PBMCs reactivation and flow cytometry: Blood collection, PBMC, myeloid cells and T cell purification, activation and flow cytometry were carried out as previously described [41].
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisThe total sample size of the study was established a priori to achieve a minimum power of 0.8 considering a large effect size (f=0.4) using Gpower 3.1 [40].

    Table 2: Resources

    Antibodies
    SentencesResources
    The following fluorochrome-conjugated antibodies were used: CD14-Violet Fluor 450 (Ref 75-0149-T100, TONBO), CD11b-PerCP-Cy5-5 (Ref 65-0112-U1, TONBO), CD62L-APC (Ref 130-113-617, Miltenyi), CD66b-APC-Cy7 (Ref 130-120-146, Miltenyi), CD54-FITC (Ref 130-104-214, Miltenyi), CD19-PE (Ref 130-113-731, Miltenyi), CD3-APC (Ref 130-113-135, Miltenyi), CD8-APC-Cy7 (Ref 130-110-681, Miltenyi), CD4-FITC (Ref 130-114-531, Miltenyi), CD27-PE (Ref 50-0279-T100, TONBO), CD28-PE-Cy7 (Ref 130-126-316, Miltenyi).
    CD62L-APC
    suggested: (Miltenyi Biotec Cat# 130-091-755, RRID:AB_244246)
    CD19-PE
    suggested: None
    CD3-APC
    suggested: None
    CD27-PE
    suggested: (Sigma-Aldrich Cat# SAB4700134, RRID:AB_10896453)
    For detection of S and N specific antibodies, a 96-well plate was coated with 5 µg/mL of the corresponding protein, followed by blocking with 1X PBS-2% BSA. 1:800, 1:250 and 1:80 sera dilutions were used for detection of anti-S antibodies, anti-N antibodies and anti-M antibodies, respectively.
    anti-S
    suggested: None
    anti-N
    suggested: None
    anti-M
    suggested: None
    Anti-human IgGs HRP-labelled antibody (ThermoFisher) was used as secondary antibody.
    Anti-human IgGs
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses: Statistical analyses were performed with GraphPad 8.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  4. Version published to 10.1101/2022.05.27.22275672v1 on medRxiv