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There are different subsets of T regulatory cells (Tregs), orchestrating critical roles in the regulation of anti-tumor immunity in colorectal cancer (CRC). In this study, we report that a high frequency of circulating CD4+FoxP3+ Tregs was associated with poorer disease-free survival (DFS), while their higher frequencies in tumor-infiltrating CD4+ Tregs was associated with better DFS. We further investigated such associations with four Tregs/T cells expressing or lacking FoxP3 and Helios (FoxP3±Helios±). For the first time, we report that a high frequency of circulating CD4+FoxP3+Helios+ Tregs was associated with poorer DFS, while a high frequency of tumor-infiltrating CD4+FoxP3-Helios- T cells was associated with poorer DFS. In the four FoxP3±Helios± T cell subsets expressing any of the immune checkpoints (ICs) investigated, we found that a high frequency of CD4+FoxP3+Helios-PD-1+ Tregs in circulation was associated with worse DFS. We also found that high frequencies of FoxP3+Helios+CTLA-4+ Tregs, FoxP3+Helios-CTLA-4+ Tregs, and FoxP3-Helios+CTLA-4+ CD4+ T cells in circulation were associated with worse DFS. In contrast, high frequencies of CD4+TIM-3+ T cells, FoxP3+Helios+TIM-3+ Tregs, and FoxP3-Helios+TIM-3+ CD4+ T cells in circulation were associated with longer DFS. Our data show that certain CD4+ Treg/T cell subsets could serve as independent predictive biomarkers in CRC patients. Identification of the exact subpopulations contributing to clinical outcomes is critical for prognoses and therapeutic targeting. [ABSTRACT FROM AUTHOR]

Rosai-Dorfman disease (RDD) is a rare disorder characterized by excessive growth of histiocytes. We present a case of a 14-year-old female with cutaneous RDD who had a subcutaneous lump on her left arm for three years. The lump became tender and progressively larger over the past year. She had no systemic symptoms, and her physical examination revealed a mobile, tender lump. Laboratory tests were normal. Surgical excision of the lump was performed, and histopathological examination confirmed RDD with the presence of epithelioid histiocytes with eosinophilic and clear cytoplasm, along with emperipolesis and positive staining for CD68, CD163, S100, and OCT2. The patient was referred for follow-up and required no further treatment. RDD can present with subcutaneous masses without systemic symptoms, and it is important to consider RDD in the differential diagnosis of such cases. Surgical excision is the main treatment, and long-term monitoring is necessary due to the potential for disease recurrence. Awareness of cutaneous RDD presentations is crucial for accurate diagnosis and management., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Al-Hashemi et al.)