Abstract A023: Evaluating Desmocollin-3 and tumor infiltrating lymphocytes in solid tumors

Abstract Introduction: Desmocollin-3 (DSC3) is a transmembrane glycoprotein. It is a p53-responsive desmosomal cadherin protein and takes part in transmembrane signaling. It is used to differentiate squamous lung cancer from non-squamous cancer. Its expression is known to be altered in various cancers. Like other adhesion molecules, it is also known to act as a barrier to tumor infiltration by immune cells (TIL). Previous studies have shown that the Mycobacterium w (Mw) vaccine, a heat-killed suspension of a non-pathogenic mycobacterium, induces a DSC3-specific cell-mediated ( CD8+ T cells) immune response. Preclinical and clinical studies have demonstrated the efficacy of Mw as a monotherapy or in combination with other therapies in DSC3-expressing tumors. These findings have motivated us to advance the potential of using Mw in various cancer types. The present study is focused on evaluating the expression levels of DSC3 in patient biopsy samples, and its correlation with TIL. Materials and methods: DSC3 protein expression was evaluated by immunohistochemistry using an anti-Desmocollin 3 monoclonal antibody from Progen (Clone: Dsc3-U114, Cat. No. 61093) in various cancers. It detects the extracellular anchor domain of DSC3. TILs were evaluated following H&E staining in the same sample. Both were calculated as tumor proportion scores as a percentage of cancer cells. The correlation between DSC3 expression and TIL was performed using Spearman correlation. Results: A total of 517 samples were evaluated, and DSC3 expression was observed in 320 (61.9%) samples with DSC3 expression levels ranging from 1% to 90%. DSC3 expression was found in 100% of cases of cervical cancer. This was followed by buccal mucosa cancer (92.1%), ovarian cancer (84.4%), squamous NSCLC (81.4%), renal cancer ( 68.2%), sarcoma (( 66.7%), non-muscle invasive bladder cancer (NMIBC) (59.3%), endometrial uterine cancer (50%), breast cancer (37.7%), non-squamous NSCLC (33.3%), and myeloma (22.7%). DSC3 was not detected in pancreatic and prostate cancer. DSC3 expression with TPS ≥25% and ≥50% was seen in 90.9% and 54.6% of Ca tongue, 80% and 40% of cervical cancer, 74.2% and 22.5% of buccal mucosal cancer, 79.7% and 73.4% of ovarian cancer, 51.2% and 27.9% of squamous NSCLC, 18.2% and 9.1% of renal cancer, and 22.2% and 5.6% of NMIBC. Sarcoma, uterine cancer, and non-squamous NSCLC had DSC3 TPS ≥25% in 33.3%, 28.6%, and 11.1%, respectively. TIL ranged from 0% to 60%. No correlation was found between DSC3 expression and TIL (Spearman's correlation coefficient = 0.19928, p (2-tailed) = 0.00058). Conclusion: DSC3 expression is seen in the majority of cancer types, and its expression level is variable. It is expressed in high proportion in the CA tongue, cervical cancer, buccal mucosa, squamous NSCLC, and ovarian cancer, with more than 50% expressing DSC3 25% or more. The analysis of the study cohort showed no correlation between DSC3 and TIL. Citation Format: Dr. Bakulesh M Khamar. Evaluating Desmocollin-3 and tumor infiltrating lymphocytes in solid tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A023.