Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers.

Regulatory T cells (Tregs) play an important role in maintaining immune tolerance and homeostasis by modulating how the immune system is activated. Several studies have documented the critical role of Tregs in suppressing the functions of effector T cells and antigen-presenting cells. Under certain conditions, Tregs can lose their suppressive capability, leading to a compromised immune system. For example, mutations in the Treg transcription factor, Forkhead box P3 (FOXP3), can drive the development of autoimmune diseases in multiple organs within the body. Furthermore, mutations leading to a reduction in the numbers of Tregs or a change in their function facilitate autoimmunity, whereas an overabundance can inhibit anti-tumor and anti-pathogen immunity. This review discusses the characteristics of Tregs and their mechanism of action in select autoimmune skin diseases, transplantation, and skin cancer. We also examine the potential of Tregs-based cellular therapies in autoimmunity.

T-Cell Mediated Immunity in Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and frequently lethal skin cancer with neuroendocrine characteristics. MCC can originate from either the presence of MCC polyomavirus (MCPyV) DNA or chronic ultraviolet (UV) exposure that can cause DNA mutations. MCC is predominant in sun-exposed regions of the body and can metastasize to regional lymph nodes, liver, lungs, bone, and brain. Older, light-skinned individuals with a history of significant sun exposure are at the highest risk. Previous studies have shown that tumors containing a high number of tumor-infiltrating T-cells have favorable survival, even in the absence of MCPyV DNA, suggesting that MCPyV infection enhances T-cell infiltration. However, other factors may also play a role in the host antitumor response. Herein, we review the impact of tumor infiltrating lymphocytes (TILs), mainly the CD4+, CD8+, and regulatory T-cell (Tregs) responses on the course of MCC, including their role in initiating MCPyV-specific immune responses. Furthermore, potential research avenues related to T-cell biology in MCC, as well as relevant immunotherapies are discussed.

Persistence of Gender Bias Over Four Decades of Surgical Training.

OBJECTIVE: Female surgeons face gender-specific obstacles during residency training, yet longitudinal data on gender bias experienced by female surgery residents are lacking. We aimed to investigate the evolution of gender bias, identify obstacles experienced by female general surgery residents, and discuss approaches to supporting female surgeons during residency training. METHODS: Between August 2019 and January 2021, we conducted a retrospective cohort study using structured telephone interviews of female graduates of the UCLA General Surgery Residency training program. Responses of early graduates (1981-2009) were compared with those of recent graduates (2010-2020). Quantitative data were compared with Fisher's exact tests and Chi-squared tests. Interview responses were reviewed to catalog gender bias, obstacles experienced by female surgeons, and advice offered to training programs to address women's concerns. RESULTS: Of 61 female surgery residency graduates, 37 (61%) participated. Compared to early graduates (N = 20), recent graduates (N = 17) were significantly more likely to pursue fellowship training (100% vs. 65%, p < 0.01) and have children before or during residency (65% vs. 25%, p = 0.02). A substantial proportion in each cohort experienced some form of gender bias (71% vs. 85%, p = 0.43). Compared to early graduates, recent graduates were significantly less likely to report experiencing explicit gender bias (12% vs. 50%, p = 0.02) but equally likely to report implicit gender bias (71% vs. 55%, p = 0.50). Female graduates across the decades advocated for specific measures to champion work-life balance in residency (51%), strengthen female mentorship (49%), increase childcare support (41%), and promote women into leadership positions (32%). CONCLUSIONS: While having children during residency has become more common and accepted over the decades, female surgery residents continue to experience implicit gender bias in the workplace. Female surgeons advocate for targeted interventions to establish systems for parental leave, address gender bias, and strengthen female mentorship.

Does Keloid Histology Influence Recurrence?

ABSTRACT: Keloids are fibroproliferative disorders characterized by high recurrence rates, with few factors known to influence the same. We conducted a study to determine whether keloid histology influences recurrence. This was a prospective longitudinal study to determine whether histopathological parameters of keloid influence recurrence. Patients with keloids managed by surgical excision were followed up at Kenyatta National Hospital between August 2018 and July 2020. The excised keloids were processed for histology using hematoxylin,/eosin, Masson, and trichrome stains. The slides were analyzed for inflammatory cells, fibroblasts, and capillary density using the hot spot technique and correlated to keloid recurrence. Postoperative follow-up was for a minimum of 1 year. A total of 90 patients with 104 keloids were recruited in the study. Overall keloid recurrence rate was 28.6%. There was a correlation between the absolute count of more than 50 per High power field of lymphocytes, fibroblasts, and macrophages with recurrence of the disease. The sensitivity and specificity for the above parameters were lymphocytes 48% and 81%, macrophages 57% and 83%, mast cells 32% and 33%, and fibroblasts 41% and 91%, respectively. There was no correlation between mast cells and vascularity status with recurrence. Routine histology should, therefore, be performed to determine these parameters. Close monitoring and second-line therapy should be considered for patients with elevated macrophages and/or lymphocytes so as to reduce the risk of recurrence.