Natural Killer Cell Dysfunction in Obese Patients with Breast Cancer: A Review of a Triad and Its Implications.

Natural killer cells (NK cells) are a crucial constituent of the innate immune system as they mediate immunity against viruses, bacteria, parasites, and most importantly, tumor cells. The exact mechanism of how the innate immune system and specifically NK cells interact with cancer cells is complex and is yet to be understood. Several factors that constitute the tumor microenvironment (TME) such as hypoxia and TGF-ß are believed to play a role in the complex physiological reaction of NK cells to tumor cells. On the other hand, several risk factors are implicated in the development and progression of breast cancer, most importantly: obesity. Cytokines released from adipose tissue such as adipokines, leptin, and resistin, among others, are also believed to facilitate tumor progression. In this study, we aimed to build a triad of breast cancer, obesity, and NK cell dysfunction to elucidate a link between these pillars on a cellular level. Directing efforts towards solidifying the link between these factors will help in designing a targeted immunotherapy with a low side-effect profile that can revolutionize breast cancer treatment and improve survival in obese patients.

Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors.

Cellular entry of SARS-CoV-2 is thought to occur through the binding of viral spike S1 protein to ACE2. The entry process involves priming of the S protein by TMPRSS2 and ADAM17, which collectively mediate the binding and promote ACE2 shedding. In this study, microarray and RNA-sequencing (RNA-seq) expression data were utilized to profile the expression pattern of ACE2, ADAM17, and TMPRSS2 in type 2 diabetic (T2D) and non-diabetic human pancreatic islets. Our data show that pancreatic islets express all three receptors irrespective of diabetes status. The expression of ACE2 was significantly increased in diabetic/hyperglycemic islets compared to non-diabetic/normoglycemic. Islets from female donors showed higher ACE2 expression compared to males; the expression of ADAM17 and TMPRSS2 was not affected by gender. The expression of the three receptors was statistically similar in young (≤40 years old) versus old (≥60 years old) donors. Obese (BMI > 30) donors have significantly higher expression levels of ADAM17 and TMPRSS2 relative to those from non-obese donors (BMI < 25). TMPRSS2 expression correlated positively with HbA1c and negatively with age, while ADAM17 and TMPRSS2 correlated positively with BMI. The expression of the three receptors was statistically similar in muscle and subcutaneous adipose tissues obtained from diabetic and nondiabetic donors. Lastly, ACE2 expression was higher in sorted pancreatic ß-cell relative to other endocrine cells. In conclusion, ACE2 expression is increased in diabetic human islets. More studies are required to investigate whether variations of ACE2 expression could explain the severity of COVID-19 infection-related symptoms between diabetics and non-diabetic patients.