Immunomodulatory features of radiotherapy in lung carcinoma

Abstract

Background: As a standard treatment modality, radiotherapy (RT) has been widely employed for cancer treatment. In addition to directly killing tumor cells, RT is known for its immunomodulatory effects. Nevertheless, the effects of ionizing radiation on immune reactions, as well as their underpinning mechanisms, are complex and remain unclear.

Methods: The immunomodulatory effects of ionizing irradiation were dynamically monitored by concomitant assessment of peripheral blood lymphocytes, and Th1 (CD3+CD4+IFN-r+), Th2 (CD3+CD4+IL-4+), Tc1 (CD3+CD8+IFN-r+) and Tc2 (CD3+CD8+IL-4+) cells, along with CD25, CD28, CTLA-4, PD-1, Foxp3, TGF-β, and IL-10 gene expression levels in 30 lung cancer patients who underwent RT.

Results: Local cancer RT activated cellular immune reactions, which was reflected by an obvious reduction of B cells and increased CD8 and NK cell amounts, and consequent increase of suppressor T cells (Ts). Further investigation showed that Th2 and Tc2 responses were significantly increased while Th1 and Tc1 were decreased.

Conclusions: The immunomodulatory effects mediated by RT are characterized by a shift from humoral to cellular immunity, significant augmentation of CD8 and Ts subpopulation, and Th2 and Tc2 responses, indicating an immuno-activating response, which might be beneficial for initial antitumor immune reactions, but may not affect the later ones. Immunomodulatory therapy should be performed upon RT to restore the immune balance for maintaining a Th1/Tc1 dominant immunity to achieve long-term anticancer immunity.

Keywords: Lung carcinoma; cellular immunity; lymphocytes; radiotherapy (RT).

Figure 1

Gene expression levels of CD25, CD28, CTLA-4, PD-1, Foxp3, TGF-β, and IL-10. (A) 17 lung cancer cases pretreatment and post-radiotherapy; (B) 13 lung cancer cases pretreatment and immediately post-therapy, and 1 month (IMRT) post-radiotherapy or 2 months (CyberKnife). IMRT, intensity-modulated radiation therapy.

Figure 2

Gene expression alterations of the 7 immune molecules in 30 lung cancer cases post-radiotherapy. Blue, upregulation after radiotherapy; Red, downregulation after radiotherapy.

Figure S1

The variation trend of the mRNA expression of seven molecules in lung cancer patients with adenocarcinoma (A) or squamous cell carcinoma (B), or performed by CyberKnife (C) or IMRT (D) therapy. Blue column, up-regulation after therapy; Red columns, down-regulation after therapy. IMRT, intensity-modulated radiation therapy.