Long-term immune dysfunction after radiotherapy to the head and neck area

Int Immunopharmacol. 2003 Aug;3(8):1093-1104. doi: 10.1016/S1567-5769(03)00013-4.


Background: Hematological side effects are not generally expected due to radiotherapy involving limited radiation fields; however, patients with squamous cell carcinoma of the head and neck (SCCH and N) receiving radiation therapy frequently have chronic intraoral infections. Xerostomia has been implicated as a cause of it, but local or systemic immune alterations are not usually considered.

Methods: With the purpose of evaluating the impact of radiotherapy treatment to different anatomic sites on immune function, 70 patients were evaluated during and after radiotherapy: 50 cases with SCCH and N, 10 with squamous cell carcinoma of the uterine cervix (SCCUC) and 10 patients with central nervous system tumors (CNS). We analyzed lymphocyte counts and T-cell subsets, and over time, their association with the presence of intracellular infections and disease-free survival.

Results: Severe lymphopenia was observed in patients with SCCUC and SCCH and N by the fifth week of treatment. Patients with CNS tumors developed mild lymphopenia. In patients with SCCH and N and UC, lower counts were seen in B cells and total T lymphocyte counts including both CD4(+) and CD8(+) cell subsets. The patients with SCCUC recovered lymphocyte counts by the 24th month but T-cell subsets lagged behind. None of the SCCH and N patients had fully recovered by 60 months of follow-up. Recurrence correlates with low lymphocyte counts.

Discussion: This work highlights the vulnerability of the head and neck area to the impact of radiotherapy as a reservoir of lymphoid cells. The possibility of recovery as a consequence of thymopoiesis and/or peripheral clonal expansion may limit the antigen-specific recognition of relevant tumor or microbial antigens and cause significant and prolonged immune alterations that may impact long-term survival.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Central Nervous System Neoplasms / immunology
  • Central Nervous System Neoplasms / radiotherapy
  • Female
  • Follow-Up Studies
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Immunologic Memory / immunology
  • Immunologic Memory / radiation effects
  • Lymphocyte Count
  • Lymphopenia / etiology
  • Lymphopenia / immunology*
  • Male
  • Middle Aged
  • Neoplasms, Squamous Cell / immunology
  • Neoplasms, Squamous Cell / radiotherapy*
  • Prospective Studies
  • Radiotherapy / adverse effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / radiation effects
  • Time Factors
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / radiotherapy