Prognostic significance of alterations in peripheral cellular and humoral immune biomarkers during radiochemotherapy in head and neck cancer patients.

Abstract

Background: The impacts of radiochemotherapy on peripheral blood cell and lymphocyte cell counts, immunoglobulin (Ig) and complement levels remain unclear. This study aims to investigate the above parameters regulated by radiotherapy (RT), induction chemotherapy (ICT) and concurrent chemotherapy (CCT) in head and neck cancer (HNC) patients.

Methods: Patients with non-metastatic HNC treated by conventional intensity-modulated radiation therapy (IMRT) were enrolled in this study. Data of peripheral blood cells, lymphocyte subpopulations, complements and immunoglobulins were collected before, during and after IMRT. And conducted regular follow-up on patients. SPSS (IBM, version 26.0), R (MathSoft, 4.0.3) and Graphpad Prism were used to perform statistical analysis and plot figures.

Results: A total of 126 HNC patients undergoing RT were enrolled in this study. Among them, 44 patients received ICT, 56 patients received CCT, and 123 patients had complete survival information. Number of white blood cells (WBCs), platelets, basophils, total lymphocytes, CD4⁺ and CD8⁺ T cells, natural killer (NK) cells, B cells declined significantly during RT. Accordingly, the ratio of help T cells to suppressor T cells (Th/Ts) and the percentages of B cells, CD4⁺ T cells also declined. There were increased levels of neutrophils and complement 4 (C4) and percentage of NK cells during RT. ICT caused significant reductions of platelets, B cells and immunoglobulin A (IgA). CCT reduced WBCs, red blood cells (RBCs), platelets, hemoglobin (HGB), granulocytes, total lymphocytes, B cells, CD4⁺ and CD8⁺ T cells, NK cells and immunoglobulin G (IgG). Generalized linear model (GLM) analysis further confirmed that RT was a risk factor for lower total lymphocytes, B cells, CD4⁺ and CD8⁺ T cells, NK cells, Th/Ts ratios, and lower percentages of B cells, CD4⁺ T cells. ICT contributed to decreased Th/Ts ratios, and immunoglobulin M (IgM) and IgA levels. As for CCT, it was an unfavorable factor for reduced total lymphocytes, B cells, CD4⁺ and CD8⁺ T cells, NK cells and IgG. Conversely, complement 3 (C3) or 4 levels were higher in patients treated with RT, ICT or CCT. Importantly, we found that HNC patients with higher lymphocytes or lymphocyte percentages like CD3⁺, CD4⁺ and CD8⁺ T cells before or after RT had a better prognosis. While higher NK cells and NK cell percentage before RT were associated with worse prognosis. In addition, higher levels of C3 and C4 before and after RT were associated with a favorable prognosis. However, higher levels of IgA, immunoglobulin E (IgE), IgG, and IgM before RT were associated with poorer prognosis.

Conclusions: To sum up, chemoradiotherapy resulted in significant alterations in peripheral immune biomarkers which in return influenced HNC patients' survival.