CD3 − CD16 − CD56 bright Immunoregulatory NK Cells are Increased in the Tumor Microenvironment and Inversely Correlate with Advanced Stages in Patients with Papillary Thyroid Cancer

Abstract

Background:

The innate immune system is the first line of defense and plays a key role in thyroid cancer development. The role of the tumor-infiltrating natural killer (NK) cells is becoming increasingly important in research and potential cancer therapies. NK cell subpopulations, CD3⁻CD16⁺CD56^dim and CD3⁻CD16⁻CD56^bright, demonstrate a significant role in the tumor immuno-surveillance process.

Methods:

We investigated the distribution of CD3⁻CD16⁺CD56^dim and CD3⁻CD16⁻CD56^bright NK subpopulations in tissue and blood samples from patients with papillary thyroid cancer (PTC) and nodular goiter (NG). Twenty-eight patients with PTC, 13 patients with NG, and 50 healthy donors were included in the study. Tissue and blood samples from all patients and blood samples from healthy donors were analyzed for CD3⁻CD16⁺CD56^dim and CD3⁻CD16⁻CD56^bright NK cells by flow cytometry.

Results:

A significant predominance of CD3⁻CD16⁺CD56^dim cells compared to CD3⁻CD16⁻CD56^bright NK cells was found in blood samples in all groups (p<0.0001 in PTC, NG, and healthy donors). Increased infiltration by CD3⁻CD16⁻CD56^bright NK cells was observed in thyroid tissue of patients with PTC, as compared to CD3⁻CD16⁺CD56^dim NK cells (p=0.046), while CD3⁻CD16⁺CD56^dim NK cells demonstrated a higher infiltration of NG tissues. CD3⁻CD16⁺CD56^dim NK cell tissue infiltration positively correlated with advanced stages of PTC. In contrast, the CD3⁻CD16⁻CD56^bright NK cell population was negatively associated with tumor stage in patients with PTC.

Conclusion:

CD3⁻CD16⁻CD56^bright NK cell infiltration seems to be associated with PTC progression. These findings contribute to a better understanding of the immune response in PTC and may lead to novel immunotherapeutic approaches in these patients.