Abstract 7065: Desmocollin3 and tumor immune infiltrate: A bioinformatics evaluation

Abstract Introduction: Desmocollin-3 (DSC3), a transmembrane glycoprotein is expressed in various cancers like squamous lung, head & neck, Cervical, Melanoma, bladder cancer etc. DSC3 is also a predictive biomarker for efficacy of Mycobacterium w (Mw) vaccine, a heat-killed suspension of a non-pathogenic mycobacterium. It induces a DSC3-specific cell-mediated (CD8+ T cells) immune response and considered to be a barrier for immune infiltrate. Efficacy of anti-PD1/PDl1 therapy depends on tumor infiltrating immune cells. Present study focuses on the key immune genes and their relationship with DSC3 gene. Materials and Methods: DSC3 and other genes encoding various immune functions (Table) were evaluated across 17 cancers using cBioPortal TCGA PAN CANCER data set. For correlation between DSC3 and other immune genes, samples with a positive Z score for DSC3 or upper quartile DSC3 (lower of two) were used. Results: DSC3 expression in Squamous lung cancer, Cancer cervix, head & neck, melanoma, colorectal cancer, mesothelioma and adenocarcinoma stomach were found to have major impact with negative Z score for majority of CD8, M1, Th1, T exhaust, M2 and Th2 genes suggesting lower infiltration of immunosuppressive and immunostimulant immune cells. Following genes had negative Z scores in all seven cancers:1. CD8 group: CD8A, CD8B, GZMA, GZMB, GZMK, GZMM, PRF1, TBX12. M1 group: CCL15, CCL20, CCR7, CXCL10, FCGR1BP, CYBB, Il15, 1l15RA3. Th1 group: CXCR3, IL274. Texhast; BTLA, LAG3, PDCD1, SLAMF6, TIGIT 5. Th2: BATF, CXCR6, SOCS1 6. M2: CD163Similar finding of lower magnitude were also seen in bladder cancer, ovarian cancer, thyroid cancer, pancreatic cancer, adenocarcinoma lung, uterine cancer, testicular germ cell cancer, renal cancer, sarcoma, hepatocellular cancer. Conclusion: DSC3 expressing tumours are likely to have lower TIL (immunostimulant as well immunosuppressive) and may not be ideal candidate for check point inhibitors. Citation Format: Bakulesh M. Khamar, Sanjay V. Malhotra. Desmocollin3 and tumor immune infiltrate: A bioinformatics evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7065.