Background: Previous studies have demonstrated the prognostic value of globulin (GLB), albumin (ALB), the ALB/GLB ratio (AGR), body mass index (BMI), hemoglobin (Hb), and prognostic nutritional index (PNI) in breast cancer. The underlying mechanism has been investigated by examining the impact of nutritional parameters on T cells, natural killer cells, and dendritic cells, but little is known about their effect on checkpoint molecules. 
Methods: Here, we investigated the correlation of mRNA expression of programmed cell death protein 1 (PD-1), cluster of differentiation 28 (CD28), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and cluster of differentiation 25 (CD25) with AGR, ALB, GLB, total protein, pre-ALB, Hb, BMI, and PNI in the peripheral blood of breast cancer patients. One hundred and three patients and 21 age- and sex-matched healthy controls were enrolled. Quantitative real-time PCR was used to test relative mRNA expression. 
Results: The results indicated that the mRNA levels of PD-1 and CD25 were 5.2- and 3.3-fold higher in patients with low AGR than in those with high AGR (P < 0.05). The mRNA levels of PD-1 were 3.5-fold higher in patients with high GLB than in those with low GLB (P < 0.05). In addition, breast cancer patients had higher expression levels of PD-1, CD28, CTLA-4, and CD25 mRNA in their peripheral blood compared with healthy volunteers (P < 0.05). 
Conclusion: These results suggest that AGR is negatively correlated with PD-1 and CD25 mRNA levels, while GLB is positively associated with PD-1 mRNA levels. Nutritional status in breast cancer patients may influence the PD-1 pathway and have implications for the optimization of cancer therapy.
Keywords: nutrition, AGR, globulin, immune checkpoint, PD-1, CTLA-4, breast cancer