2026 Poster Presentations
P300: ASSESSING THE TUMOR IMMUNE MICROENVIRONMENT OF SINONASAL NUT CARCINOMA
Yoko Takahashi, PhD1; Diana Bell, MD2; Jennifer L Anderson, MD, PhD1; Jared Burks, PhD1; Matheus Sewastjanow-Silva, MD1; Shirley Y Su, MD1; Ehab Y Hanna, MD1; 1The University of Texas MD Anderson Cancer Center; 2The University of Pittsburgh Medical Center
Background: NUT carcinoma is a highly aggressive cancer defined by rearrangements of the NUT midline carcinoma family member 1 gene. Despite aggressive treatment, patients have a median survival of only seven months. Currently, there is no standard treatment for NUT carcinoma, highlighting the need for new experimental models and improved treatment strategies. In previous research, we established and characterized two novel sinonasal NUT carcinoma cell lines from a surgical specimen. To gain a deeper understanding of the disease, we conducted a multiplex immunofluorescence study on the surgical specimen from which these cell lines were derived.
Materials and Methods: A formalin-fixed, paraffin-embedded surgical specimen from a 28-year-old man who was diagnosed with T4bN0M0 sinonasal NUT carcinoma was used in this study. The patient underwent two cycles of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil at another institution, followed by surgical resection at the University of Texas MD Anderson Cancer Center. Opal 7-color multiplex immunofluorescence was performed on the surgical specimen, using antibodies for pan-cytokeratin (CK, clone 80), CD3, CD8, PD-L1, CD68, CD56/NCAM (an NK cell marker), and DAPI. Tissue identification, marker detection, and data extraction were conducted using QuPath (version 0.5.1). Tumor cells with low CK expression were categorized as 'CKlow' cells, and their proportion within the tumor was calculated as CKlow / (CKlow + CK+) x 100.
Results: Fifty-four percent of the tumor cells were classified as CKlow, indicating heterogeneity within this tumor sample. CD8+ tumor-infiltrating lymphocytes were present at only 0.14%, suggesting that this specimen exhibits a less immunogenic 'cold' tumor profile. The percentage of PD-L1-positive tumor cells, which is associated with a better response to immunotherapy in various tumor types, was less than 0.2%. Furthermore, the percentage of CD68+PD-L1+ macrophages, another indicator for response to certain types of immunotherapies, was found to be less than 5%.
Conclusions: The sample of sinonasal NUT carcinoma that we analyzed exhibited heterogeneous cytokeratin expression and low immunogenic characteristics. Given that NUT carcinoma is primarily driven by a single fusion oncoprotein, it has a low tumor mutational burden, which may align with these findings. Since conventional treatments for NUT carcinoma, such as chemotherapy and radiation therapy, have shown very limited success, it is essential to develop strategies to address the tumor immune microenvironment and to incorporate immunotherapy and potential new targetable therapies effectively. We plan to create an advanced panel with additional markers and include more tumor samples to further investigate the biology of sinonasal NUT carcinoma in our future studies.