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

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.

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.

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.

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.