The University of Toledo Translation Journal of Medical Sciences 
Endocrinology Abstract, Department of Medicine Research Symposium UTJMS 2023 May 05; 11(1):e1-e1 

Double Negative T Cell Proportion of CD3+ 
Cells Present in the Thyroid 
Microenvironment is an Immunogenomic 
Marker for Predicting Thyroid Cancer 
Brennon Richard1*, Michael Robert Stuckert1, Rodis Paparodis, MD1, Shafiya Imtiaz 
Rafiqi, DVM, PhD1, Azra Niaz, MD1, Nancy Salim1, Juan C. Jaume, MD1, 
Shahnawaz Imam, DVM, PhD1

1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, 
The University of Toledo, Toledo, OH 43614 
2Division of, Department of Medicine, The University of Toledo, Toledo, OH 43614 
3Division of, Department of Medicine, The University of Toledo, Toledo, OH 43614 

*Corresponding author: Brennon.Richard@rockets.utoledo.edu

Published: 05 May 2023 

Thyroid cancer is becoming increasingly relevant in the growing population and has been seeing a 
greater incidence of diagnosis since the early 1980s. While there has been an increase in diagnosis, there 
has not been any significant advancement in the quality or sensitivity of screening methods. Current 
guidelines recommend repeat biopsy in these patients because they lack any guidance if patients 
continue to yield unclear or contradictory pathology. Current ATA recommendations state that these 
patients should receive diagnostic surgery which results in the removal of the entire thyroid gland. It is 
estimated that 60-75% of these surgeries end up removing benign lesions. Yet with the current methods 
of diagnosis, it is impossible to determine the prognostic status of every thyroid nodule without 
thyroidectomy for patients with unspecified pathology. We have found a diagnostic profile that lends a 
greater sensitivity and specificity using the microenvironments of the tumor cells. A fine needle aspirate 
sample from patients with thyroid nodules was analyzed via flow cytometry. Using this data, we 
characterized the lymphocytic environment of malignant tumors expressing a large population of T cells 
which are neither expressing CD4 nor CD8 (CD3+CD4-CD8-) known as double negative lymphocytes 
(DN T) cells. A profile of >9.14% DNT cells was shown to indicate malignancy with a sensitivity of 
96.6% and specificity of 100%. Therefore, measurement of tumor microenvironment cell populations 
serves as an extremely effective method for thyroid nodule risk assessment. This would be instrumental 
in cutting back the number of unnecessary surgeries and avoiding excessive patient hardship resulting 
from surgery or postsurgical care. Clearly, the microenvironment holds significance in the instance of 
malignant modules, and they reflect the behavior of the tumor. Using High-throughput gene expression 
analysis, we will analyze the mRNA expression of DN T cells present in the microenvironment. Using 
the information gathered, we will design a profile of markers that indicate malignancy. Furthermore, our 
group is working on amplifying DN T cell markers on a PCR-based platform to allow a more 
economically viable diagnostic test. 

https://dx.doi.org/10.46570/utjms.vol11-2023-651 

https://dx.doi.org/10.46570/utjms.vol11-2023-651
mailto:Brennon.Richard@rockets.utoledo.edu