Applying Circulating CD4CD25FOXP3 T Regulatory Cells and Interleukin 10 as a Measurable Clinical Predictor of Immune Status in Cancer Patients

Abstract

Infection is a major cause of death in cancer patients. Most cancer patients have deregulated immune responses. Immune tolerance to cancer cells occurs mainly in the peripheral immune system which are regulated by Treg cells. Peripheral Treg cell counts increase with advancing tumor stage in head, neck, and lung squamous cell carcinomas (SCC). CD4CD25FOXP3 Treg cells are a subset of Treg cells that decrease IL-2 levels, secrete IL-10 and suppress CD8 T cells. We aim to determine the relationship between circulating CD4CD25FOXP3 Treg cells and the ability of patients with SCC of the head, neck, and lungs to mount an immune response. We hypothesize that compromised immune status in cancer patients are mediated through increased level of Treg cells and baseline IL-10 level. All patients with unresectable SCC of the head, neck and lungs requiring chemotherapy and/or radiation were included in this prospective observational study. Blood samples to measure levels of Treg cells, IL-2, and IL-10 were collected at the beginning of study enrollment and at the end of therapy or 6 months post enrollment, whichever occurred first. Subjects were followed for 12 months to track number of infections and treatment days. Although 23 eligible patients were enrolled, 2 patients died before the 12 month set of labs were obtained. Correlation analysis was conducted on 21 subjects who survived. Survival (COX regression) and ROC curve analysis were conducted on the 23 subjects. Correlation analysis showed that values for baseline CD4 T cells, baseline IL-10, and end of treatment IL-10 had a positive correlation with patient status (p = 0.05, 0.04, 0.04 respectively). Additionally, IL-10 baseline had a positive correlation with number of infections at 12 months (p=0.05). COX regression analysis revealed that IL-10 at baseline increases the risk of infection (p= 0.02; OR = 1.3). An IL-10 baseline level of 8.5 or greater demonstrates a 67% sensitivity and 89% specificity for predicting infection (AUC = 0.856). Currently there is no established measurable clinical indicator to assess a cancer patient’s immune status. Thus, making it difficult to predict which subset of cancer patients are at a higher risk of infection. The analysis of patients with SCC of the head, neck, and lungs in our study identified IL-10 levels, not Treg cell count to be a better reflection of immune status. An IL-10 baseline level of 8.5 may be an acceptable cut off point to predict risk of infection in this patient population who are undergoing cancer treatment.