The genomic sequencing classifier demonstrates high sensitivity and accuracy for identifying benign nodules. Its 36% increase in specificity compared with the gene expression classifier potentially increases the number of patients with benign nodules who can safely avoid unnecessary diagnostic surgery.
Immune profiling has been widely used to probe mechanisms of immune escape in cancer and identify novel targets for therapy. Two emerging uses of immune signatures are identification of likely responders to immunotherapy regimens among individuals with cancer or to understand the variable responses seen among subjects with cancer in immunotherapy trials. Here the immune profiles of six murine solid tumor models (CT26, 4T1, MAD109, RENCA, LLC, and B16) were correlated to tumor regression and survival in response to two immunotherapy regimens. Comprehensive profiles for each model were generated using quantitative RT-PCR, immunohistochemistry, and flow cytometry techniques, as well as functional studies of suppressor cell populations (Treg and MDSC), to analyze intratumoral and draining lymphoid tissues. Tumors stratified as highly or poorly immunogenic, with highly immunogenic tumors showing significantly greater presence of T-cell co-stimulatory molecules and immunosuppression in the tumor microenvironment. An absence of tumor-infiltrating CTL and mature DC was seen across all models. Delayed tumor growth and increased survival with suppressor cell inhibition and tumor-targeted chemokine +/− DC vaccine immunotherapy was associated with high tumor immunogenicity in these models. Tumor MHC class I expression correlated with overall tumor immunogenicity level and was a singular marker to predict immunotherapy response with these regimens. By using experimental tumor models as surrogates for human cancers, these studies demonstrate how select features of an immune profile may be utilized to identify patients most likely to respond to immunotherapy regimens.
With advancing age, the prevalence of clinically relevant thyroid nodules increases, whereas the risk that such nodules are malignant decreases. Nonetheless, when thyroid cancer is detected in older individuals, a higher-risk histological phenotype is more likely. These data provide insight into the clinical paradox that confronts physicians managing this common illness.
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