T-Cell Lymphopenia Linked to Poor Prognosis in Advanced Thyroid Cancer

Katrin Rabold, MSc

Katrin Rabold, MSc

Recently published data from a retrospective study suggest that patients with thyroid cancer who have T-cell lymphopenia are more likely to have aggressive tumors. Investigators believe this information can be used to identify potential therapeutic targets in these patients.

Historically, patients with aggressive forms of nonmedullary thyroid cancer, in particular, patients with anaplastic thyroid cancer (ATC), have been shown to have an abundant infiltration of immune cells, which correlates with a poor prognosis. However, little has been known about levels of circulating immune cells in advanced thyroid cancer.

“In this study, we showed for the first time that the percentage of CD3-positive, CD4-positive, and CD8-positiveT cells is lower in patients with advanced metastatic thyroid cancer compared with healthy controls. Furthermore, CD3-positive and CD4-positive T‐cell lymphopenia was associated with poor prognosis. A similar, yet less pronounced, trend was seen for CD8-positive T‐cell levels,” a group of investigators, led by Katrin Rabold, MSc, of Radboud University Medical Center, wrote in their report, which was recently published inThe Oncologist.

To perform the study, the investigators quantified T cells and myeloid-derived suppressor cell (MDSC) levels in the peripheral blood of 9 patients with advanced thyroid cancer and 9 healthy individuals.

The median age of patients and healthy controls was 69 years (range, 55-81) and 59 years (range, 30-63), respectively, and 67% of both groups were male. A majority of the patients had ATC histology and T4N1 stage disease. Five of the patients had undergone at least a total thyroidectomy and lymph node dissection and been treated with radioactive iodine treatment prior to inclusion in the study.

Findings showed that lower percentages of CD3-positive, CD3-positive CD4-positive, and CD3-positive CD8-positive T cells were seen in the thyroid cancer group. Additionally, both short-term thyroid cancer survivors (survival ≤1 month) and long-term survivors (survival >1 month) had a lower percentages of CD3-positiveand CD4-positive cells. Compared with long-term survivors, the short-term survivors had lower levels of CD3-positiveand CD4-positive. Findings for CD8-positive T cells followed a similar trend.

Findings also showed that patients in the thyroid cancer group did not have increased MDSCs, defined as CD33-positive MHC-II-negative cells and subdivided into CD14-positive monocytic and CD15-positive polymorphonuclear subpopulations, compared with the healthy control group. However, the percentage of polymorphonuclear MDSCs was higher in the thyroid cancer patients classified as short-term survivors. No difference was seen in the percentage of regulatory T cells (Tregs) between patients and controls or between short- and long-term survivors.

The investigators noted that complete lymphopenia, and specifically T-cell lymphopenia, have been linked to poor prognosis in several other cancer types, including melanoma and head and neck cancer. The underlying cause of T-cell lymphopenia could be increased T-cell apoptosis, and possibly concomitant decreased homeostatic proliferation of T cells, a decreased thymic output, or redistribution of T cells to the tumor site, they wrote.

Although 2 prior studies found that MDSC levels were increased in the blood of patients with ATC, or predominantly papillary thyroid cancer, the discrepancies could be due to differences in patient populations and markers used to define MDSCs among the studies, the investigators explained.

Potential limitations of this study, the investigators wrote, could include the fact that some patients on the study previously received radioactive iodine treatment (n = 5) and 2 long-term survivors additionally received external beam radiation, which are treatments known to decrease white blood cell counts; however, higher T-cell counts were found in the long-term survivor group, which the investigators believed strengthened their findings.

“Although further validation is needed, our results demonstrate that T‐cell lymphopenia identifies patients with thyroid cancer with a poor prognosis. Therefore, monitoring T‐cell blood levels may provide additional information on prognosis in patients with thyroid cancer. Extending these investigations to larger series could help us understand the complex changes taking place during tumor progression and might influence therapeutic choices in the future,” the investigators concluded. They suggested that treatment with interleukin or an anti—CTLA-4 antibody could be an option for these patients to help to correct the quantitative deficit of T cells.

Reference:

Rabold K, Gielen PR, Kers-Rebel, ED, et al. T-Cell Lymphopenia in Patients with Advanced Thyroid Carcinoma is Associated with Poor Prognosis.The Oncologist. 2019;24(3):e106-e110. doi:10.1634/theoncologist.2018-0422.