Ectopic thyroid is an uncommon condition defined as the presence of thyroid tissue at a site other than the pretracheal area. When the process of embryologic migration is disturbed, aberrant thyroid tissue may appear. In most cases, ectopic thyroid is located along the embryologic descent path of migration as either a lingual thyroid or a thyroglossal duct cyst. In rare cases, aberrant migration can result in lateral ectopic thyroid tissue. Approximately 1 to 3% of all ectopic thyroids are located in the lateral neck. Ectopic tissue frequently represents the only presence of thyroid tissue; a second site of orthotopic or ectopic thyroid tissue is found in other cases. The presentation of ectopic thyroid as a lateral mass should be differentiated from metastatic thyroid cancer; other differential diagnoses include a submandibular tumor, branchial cleft cyst, carotid body tumor, and lymphadenopathy of various etiologies. In addition to the history and physical examination, the workup for a patient with a submandibular mass suspicious for ectopic thyroid should include (1) technetium-99m or iodine-131 scintigraphy, (2) ultrasonography and either computed tomography or magnetic resonance imaging, (3) fine-needle aspiration biopsy, and (4) thyroid function testing. No treatment is required for asymptomatic patients with normal thyroid function and cytology, but hypothyroid patients should be placed on thyroid hormone replacement therapy. Most cases are diagnosed postoperatively. Surgical treatment of ectopic thyroid should be considered when a malignancy is suspected or diagnosed, when the patient is symptomatic, or when thyroid suppression therapy fails.
Background: Cytokines have been FDA approved for cancer immunotherapy for treatment of metastatic melanoma and renal carcinoma for over 30 years (1, 2). To overcome stability and toxicity limitations seen with high dose cytokine immunotherapy, we developed a delivery platform, called cytokine factories, composed of genetically engineered epithelial cells encapsulated in biocompatible polymers. These clinically translatable cytokine factories are able to safely deliver high local doses of pro-inflammatory cytokines, such as interleukin-12 (IL12), and allow for controlled and predictable dosing in vivo. Results: Tumor-adjacent administration of IL12-based cytokine factories in vivo created a high local cytokine concentration (IP space) without substantial leakage into the systemic circulation. In addition, administration of cytokine factories in combination with anti-PD1 checkpoint inhibitors caused reduction of tumor burden by over 60% when delivered as a monotherapeutic to mice with metastatic melanoma (3). Further, when administered in combination with local anti-PD1 checkpoint inhibitors, these cytokine factories led to reduction of intraperitoneal tumor burden by over 80% after only 10 days of treatment. Finally, we evaluated the ability of this therapy to treat pancreatic tumors which are notoriously known to be resistant to immunotherapy. We found that the median survival for control animals was 45 days. However, 8/8 of animals treated with IL12 cytokine factories survived throughout the duration of the study (110 days), demonstrating a significant extension of overall survival time. Conclusions: Our findings demonstrate efficacy of cytokine factories as single agent and combination therapeutics in preclinical animal models and provide rationale for future clinical testing for the treatment of metastatic peritoneal cancers in humans. References: (1) H. Choudhry, N. Helmi, W.H. Abdulaal, M. Zeyadi, M.A. Zamzami, W. Wu, M.M. Mahmoud, M.K. Warsi, M. Rasool, M.S. Jamal, Prospects of IL-2 in Cancer Immunotherapy, Biomed Res Int, 2018 (2018) 9056173. (2) D.F. McDermott, M.B. Atkins, Interleukin-2 therapy of metastatic renal cell carcinoma–predictors of response, Semin Oncol, 33 (2006) 583-587. (3) N.E. Reticker-Flynn, W. Zhang, J.A. Belk, P.A. Basto, N.K. Escalante, G.O.W. Pilarowski, A. Bejnood, M.M. Martins, J.A. Kenkel, I.L. Linde, S. Bagchi, R. Yuan, S. Chang, M.H. Spitzer, Y. Carmi, J. Cheng, L.L. Tolentino, O. Choi, N. Wu, C.S. Kong, A.J. Gentles, J.B. Sunwoo, A.T. Satpathy, S.K. Plevritis, E.G. Engleman, Lymph node colonization induces tumor-immune tolerance to promote distant metastasis, Cell, 185 (2022) 1924-1942 e1923. <![endif]→ Citation Format: Amanda Nash, Bertha Castillo, Danna Murungi, Nathan Reticker-Flynn, Omid Veiseh. Cell-generated IL12 combined with PD-1 inhibition produces local and abscopal immune activation to eradicate metastatic melanoma and pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB101.
Pancreatic cancer is often diagnosed at advanced stages and responds poorly to chemotherapy. Because high tumor T cell infiltration corresponds with better clinical outcomes in pancreatic cancer patients, immunotherapy has gained significant interest over the last decade for the treatment of recurrent pancreatic cancer. IL-12 is a proinflammatory cytokine with pleiotropic effects including activation of CD8+ T cells and NK cells. Unfortunately, systemic high dose IL-12 administration led to severe toxicities in clinical trials which has limited further development of this cytokine as a cancer therapeutic. To address this limitation, we developed an implantable cytokine delivery platform to allow for local administration of IL-12. These cytokine factories, composed of genetically engineered epithelial cells encapsulated in biocompatible polymers, allow for safe and controlled dosing in vivo. Tumor adjacent administration of IL-12-based cytokine factories caused reduction of intraperitoneal pan02 tumor burden by 80% after only 1 week of treatment in mice with pancreatic cancer. Single cell RNAseq of the tumor adjacent immune cells at this time point showed 2x more T and NK cells present in the IL-12 treated mice than untreated mice suggesting modulation of the tumor microenvironment via immune cell infiltration. Importantly, the necessary IL-12 dose was well tolerated in all mice without signs of toxicity for 180 days. In efforts to evaluate the translatability of this platform, we further tested IL-12-based cytokine factories in a non-human primate. The cytokine factories produced a high local IL-12 concentration without substantial leakage into the systemic circulation and were well tolerated by the primates as shown by the lack of fever or weight loss, as well as the lack of renal or liver toxicity. Our findings highlight the therapeutic potential of IL-12 treatments when administered locally via cytokine factories in preclinical animal models. Further, these findings provide rationale for future development and clinical testing of cytokine factories for treatment of a wide range of metastatic peritoneal cancers in humans. Citation Format: Amanda Nash, Samira Aghlara-Fotovat, Bertha Castillo, Annie Nguyen, Andrew Cui, Andrea Hernandez, Peter Rios, Sofia Ghani, Ira Joshi, Chunyu Xu, Rahul Sheth, Weiyi Peng, Jose Oberholzer, Amir Jazaeri, Omid Veiseh. IL-12-based cytokine factories modulate tumor microenvironment to eradicate pancreatic tumors in mice and are well tolerated in non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3547.
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