# Possible role of pre-vaccination T-lymphocyte subpopulations in the antibody response to COVID-19 vaccines in children undergoing chemotherapy

**Authors:** Csaba Péterfia, Zsolt I. Komlósi, Zoltán Pós, Nikolett Lupsa, Nóra Fekete, Katalin Böröcz, Timea Dergez, Evelin A. Leibinger, Noémi Benedek, Ágnes Vojcek, Bence Horváth, Vita Vertike, Krisztina Csanádi, Péter Hauser, Lilla Györgyi Tiszlavicz, Dániel János Erdélyi, Edit Ágota Brückner, Sándor Szabó, Nikolett Jusztina Beniczky, Timea Berki, Gábor Ottóffy

PMC · DOI: 10.3389/fimmu.2026.1728845 · Frontiers in Immunology · 2026-02-05

## TL;DR

This study explores how pre-vaccination T-cell levels in children with cancer affect their antibody response to the SARS-CoV-2 vaccine.

## Contribution

The study is the first to explore the association between pre-vaccination T-lymphocyte subpopulations and antibody response to the SARS-CoV-2 vaccine in pediatric oncology patients.

## Key findings

- A higher baseline of CD3+CD56+ T cells and CD56+ NK cells was linked to a better seroconversion rate.
- CD4+ and CD4+CD3+CD56+ T cells showed a positive association with stronger antibody responses.
- The study found a similar pattern to previous findings with influenza vaccines, suggesting a role for CD3+CD56+ T cells in vaccine response.

## Abstract

In a previous study, we found a possible connection between pre-vaccination CD3+CD56+ T cells and seroresponse to influenza vaccination in immunosuppressed patients. Decreased circulating CD3+CD56+ T cells have been described in severe COVID-19, but their role in vaccination is unknown. This study evaluated the humoral immune response after SARS-CoV-2 vaccination in children with cancer following two doses of the BNT162b2 mRNA vaccine. We investigated the relationship between cellular immunity (including CD3+CD56+ T cells) and the post-vaccination antibody response.

A multicenter, prospective cohort study was completed by recruiting patients receiving chemotherapy and healthy controls, who received two doses of the BNT162b2 mRNA vaccine. Flow cytometric analysis of peripheral blood lymphocyte subpopulations was performed before vaccination; serum anti-SARS-CoV-2 IgG was measured before vaccination and 21–28 days after the second vaccination. We evaluated the relationship between various cellular parameters before vaccination and antibody response.

Serological response was assessed in 20 oncology patients and 13 healthy controls. The seroconversion rate was 55% among oncology patients and 92.3% among healthy controls (p = 0.023). Geometric mean fold increase (GMFI) of the titers was 6.69 and 41.64 (p = 0.011), respectively. Flow cytometric analysis revealed a significantly higher seroconversion rate in patients with higher baseline CD3+CD56+ T cell (p = 0.044) and CD56+ NK (p = 0.038) cell counts. Based on GMFI, we found a positive association between a greater antibody response and higher baseline CD4+ (p = 0.007), CD4+CD3+CD56+ (p = 0.019), and CD4+ MAIT (p = 0.010) cell counts, as well as a higher CD4/CD8 ratio (p = 0.029).

Our study suggests that an adequate humoral immune response can be induced by the SARS-CoV-2 mRNA vaccine in pediatric oncology patients. We explored for the first time the possible association between pre-vaccination T lymphocyte subpopulations (CD3+CD56+, CD56+ NK, CD4+, CD4+CD3+CD56+ cells) and the antibody response to the COVID-19 vaccine. We have similar observations as previously reported with influenza vaccination, suggesting that CD3+CD56+ T cells may be involved in the immune response to SARS-CoV-2 vaccines. We highlight the connection between pre-vaccination CD4+ MAIT cell populations and the antibody response.

## Linked entities

- **Diseases:** cancer (MONDO:0004992), SARS-CoV-2 (MONDO:0100096), COVID-19 (MONDO:0100096)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, KLRC2 (killer cell lectin like receptor C2) [NCBI Gene 3822] {aka CD159c, NKG2-C, NKG2C}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}, KLRB1 (killer cell lectin like receptor B1) [NCBI Gene 3820] {aka CD161, CLEC5B, NKR, NKR-P1, NKR-P1A, NKRP1A}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, CD1D (CD1d molecule) [NCBI Gene 912] {aka R3, R3G1}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, MR1 (major histocompatibility complex, class I-related) [NCBI Gene 3140] {aka HLALS}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}
- **Diseases:** influenza (MESH:D007251), respiratory disease (MESH:D012140), swelling (MESH:D004487), cancer (MESH:D009369), seroconversion (MESH:D006679), fatigue (MESH:D005221), hematological malignancies (MESH:D019337), fever (MESH:D005334), PID (MESH:D000081207), viral infection (MESH:D014777), Deaths (MESH:D003643), acute lymphoblastic leukemia (MESH:D054198), COVID-19 (MESH:D000086382), infection (MESH:D007239), muscle pain (MESH:D063806), TD (MESH:D004409), oncology (MESH:D000072716), TB (MESH:D014390), HIV (MESH:D015658)
- **Chemicals:** EDTA (MESH:D004492), FITC (MESH:D016650), Cy5.5 (MESH:C098793), 5-OP-RU (-), riboflavin (MESH:D012256)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Qubevirus faecium (species) [taxon 39804], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Gammacoronavirus (genus) [taxon 694013], Human immunodeficiency virus 1 (no rank) [taxon 11676], Human immunodeficiency virus (species) [taxon 12721], Macaca mulatta (rhesus macaque, species) [taxon 9544], Homo sapiens (human, species) [taxon 9606], Adenoviridae (family) [taxon 10508], Simian immunodeficiency virus (no rank) [taxon 11723]

## Full text

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## Figures

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## References

75 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916594/full.md

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Source: https://tomesphere.com/paper/PMC12916594