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.

(1) Background: the present review provides a comprehensive and up-to date overview of the potential exploitation of fasting as an anticancer strategy. The rationale for this concept is that fasting elicits a differential stress response in the setting of unfavorable conditions, empowering the survival of normal cells, while killing cancer cells. (2) Methods: the present narrative review presents the basic aspects of the hormonal, molecular, and cellular response to fasting, focusing on the interrelationship of fasting with oxidative stress. It also presents nonclinical and clinical evidence concerning the implementation of fasting as adjuvant to chemotherapy, highlighting current challenges and future perspectives. (3) Results: there is ample nonclinical evidence indicating that fasting can mitigate the toxicity of chemotherapy and/or increase the efficacy of chemotherapy. The relevant clinical research is encouraging, albeit still in its infancy. The path forward for implementing fasting in oncology is a personalized approach, entailing counteraction of current challenges, including: (i) patient selection; (ii) fasting patterns; (iii) timeline of fasting and refeeding; (iv) validation of biomarkers for assessment of fasting; and (v) establishment of protocols for patients’ monitoring. (4) Conclusion: prescribing fasting as anticancer medicine may not be far away if large randomized clinical trials consolidate its safety and efficacy.