Impact of chemotherapy on humoral and cellular immune responses to COVID-19 vaccination in patients with solid tumors

Front Immunol. 2025 Sep 25:16:1664072. doi: 10.3389/fimmu.2025.1664072. eCollection 2025.

Abstract

Introduction: Despite SARS-CoV-2 pandemic has subsided, vaccine response profiling in patients with cancer remains critical.

Methods: We longitudinally assessed humoral and cellular immunity in adults with solid tumours treated with chemotherapy (ChT) or non-ChT regimens after two mRNA vaccine doses plus booster, compared with vaccinated cancer-free controls, naturally infected (convalescent) subjects including both patients with cancer and cancer-free individuals, and unvaccinated/uninfected individuals with or without cancer as a baseline reference.

Results: Anti-Spike IgG titres matched cancer-free controls, but anti-RBD titres and neutralising activity were consistently lower in cancer post-vaccination, most markedly with ChT, and declined faster over 4-6 months. Boosters restored IgG, yet gains were smaller in ChT recipients. Cellular analyses revealed sustained and booster-enhanced Spike-specific B cells in all groups; however, ChT exposure was associated with reduced CD27 expression on these cells, suggesting impaired activation and memory maturation.

Discussion: These findings support tailored immune monitoring and vaccination strategies in oncology and identify CD27 downregulation as a novel B-cell dysfunction detected by high-dimensional immunophenotyping.

Keywords: SARS-CoV-2; high-dimensional; memory B cells; seroconversion; solid tumors; unbiased immunophenotyping; vaccinations.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antineoplastic Agents* / therapeutic use
  • B-Lymphocytes / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunity, Cellular* / drug effects
  • Immunity, Humoral* / drug effects
  • Immunization, Secondary
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Vaccination

Substances

  • COVID-19 Vaccines
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Immunoglobulin G
  • Antineoplastic Agents
  • spike protein, SARS-CoV-2
  • Antibodies, Neutralizing