OR09-1 Decoding Cancer Immunoediting of Tumor Microenvironment Provides Immunogenomic Marker for Thyroid Cancer Screening

: Thyroid cancer will become 4th most common cancer in women by 2030. Thyroid cancer is the most prevalent endocrine malignancy of women with an age-standardized rate of 10.1/100,000 while in men it is 3.1/100,000. The microenvironment of thyroid cancer has a high degree of immune invasion, characterized by the presence of T effector (Teff, CD4, and CD8) cells. In our previous study based on 127 human FNA thyroid samples, we reported a dominant T cell species characterized by the deficiency of CD4 and CD8 expression (CD3+CD4-CD8-) Double Negative (DN) T cells, seem to have a regulatory function towards thyroid cancer immune tolerance (1-3). Here, in another cohort study (46 patients), FNAs of thyroids showed that DN T-cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer patients (post-operatively confirmed diagnosis by an academic pathologist), and if the DN T cell population exceeded our defined threshold (>9.14%), it indicated a high likelihood of cancer presence (96.6% sensitivity, 95% CI, 0.915 to 1.000). Conversely, DN T cells below the threshold (<9.14%) provide 100% specificity in predicting benignity of thyroid nodules. This study identifies DN T cell quantification as an accurate rule-out test. The high specificity of the test is promising since it abolishes false-positive diagnoses and unnecessary surgical procedures. Current molecular diagnostic testing, based on the identification of tumor gene mutations in FNA samples usually reduces the risk of cancer rather than guarantee the absence of cancer which leads to 70% of unnecessary thyroidectomies. The present study proposes DN T cell quantification as a diagnostic signature for thyroid cancer. Its integration with RNA transcriptomics may provide a simplified technology for thyroid cancer screening and active surveillance. REFERENCES: 1. Imam S, Paparodis R, Sharma D, et al. 2014 Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity. EndocrRelat Cancer 21. 2. Imam S, Dar P, Paparodis R, et al. 2019 Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer. J Immunother Cancer 7. 3. Imam S, Jaume J C 2021 Stratifying risk of malignancy in indeterminate thyroid nodules and immuno-genomic markers for early detection of thyroid cancer. International Application No. PCT/US2021/012057, Publication Number WO/2021/138661 Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.