Effects of Radioactive Iodine on the Immune System in Thyroid Cancer

Effects on the Systemic Innate Immune System by Radioactive Iodine Treatment in Non-medullary Thyroid Cancer Patients

Blood will be drawn 1 month before and 2 month after regular radioactive iodine treatment. Monocytes will be isolated. The three main outcomes are whole blood counts, cytokine production upon in vitro stimulation of monocytes and in vitro ROS production by monocytes. These results are compared between patients treated in adjuvant setting and patients treated for persistent structural disease, and between pre- and post-treatment status.

Earlier studies have shown that, particularly advanced, thyroid carcinomas are highly immunogenic tumors. The immune system is involved in both pathogenesis and progression of thyroid carcinoma (TC), as in other malignancies. For example, it is known that increased tumor infiltration with tumor-associated macrophages is associated with decreased survival in TC patients. In a previous study from our group, changes in the programming of myeloid immune cells were identified in newly diagnoses TC patients. That study showed that upon stimulation, cytokine production was decreased in monocytes from TC patients when compared to monocytes from healthy volunteers or from patients with benign thyroid tumors. Also, reactive oxygen species (ROS) production (known to be tumorigenic) from monocytes was increased in TC patients when compared to healthy volunteers. In the mentioned study, several effects of radioactive iodine (RAI)-treatment, after surgery, on the systemic immune system were observed. For instance, lymphocyte counts were significantly reduced after treatment with RAI, an effect also observed in other studies. Moreover, after RAI-treatment, ROS levels produced by monocytes decreased to levels similar to those produced by monocytes of healthy controls. Although, the effect of RAI-treatment on ROS-production was less pronounced than that of surgery. There was no clear effect of RAI-treatment on the cytokine production capacity. However, it should be noted that in most patients in this study RAI was administered in a setting of remnant ablation, meaning that only a low dose of RAI was administered and that only a very low amount (or none) of cancer cells were present at the time of administration. Furthermore, the number of included patients was too low to perform subgroup analyses. The current study aims to assess the effect of RAI-treatment in patients with structural disease, as a higher dose of beta-radiation will be present in these patients, and compare these effects to that in patients treated with RAI in an adjuvant setting.

The investigators hypothesize that RAI-treatment will have a more pronounced effect on the systemic innate immune system in patients with structural disease when compared to patients treated in an adjuvant setting. This study will give us more insights in the interplay between RAI and the immune system in patients with TC.

The aim of the study is to assess the effect of RAI-treatment on the innate immune system in TC patients and to compare these effects between patients with and without structural disease in a prospective explorative study.

Inclusion Criteria:

• Pathologically confirmed non-medullary thyroid cancer
• Undergoing radioactive iodine treatment in an adjuvant setting or for persistent structural disease
• Aged ≥ 18 years

Exclusion Criteria:

• Inflammatory or infectious comorbidities
• Using medication interfering with the immune system
• Pregnancy
• A self-reported alcohol consumption of >21 units per week
• Other active malignancies, defined as malignancies not in complete remission for <2 years
• Previous systemic anti-cancer treatment such as chemotherapy, targeted therapy, radiotherapy or immunotherapy within 3 years before study procedures