5/31/2023 0 Comments Subree subramarian![]() By RNA-Seq, CD38 was highly expressed by LLC1 tumor cells and, therefore, anti-CD38 antibody treatment was combined with L82-pulsed DC vaccination. ![]() In contrast, DCs pulsed with LPs induced CD4 + and CD8 + T cell responses and one of them, designated L82, delayed LLC1 growth in vivo. However, they failed to inhibit LLC1 growth when incorporated into a cancer vaccine. A total of 2536 missense mutations were identified in LLC1 and of 132 candidate neoantigen short peptides, 25 were found to induce CD8 + T cell responses. Dendritic cell (DC)-based vaccination strategies were developed using candidate neoantigen long peptides (LPs). Whole-exome and RNA sequencing to predict neoantigen expression was performed on the LLC1 cell line which forms “cold” tumors in mice. AbstractĪn important factor associated with primary resistance to immune-checkpoint therapies (ICT) is a “cold” tumor microenvironment (TME), characterized by the absence of T cell infiltration and a non-inflammatory milieu. Thus, the future direction of ICT is combination immunotherapy. An appropriate vaccination strategy combining neoantigen peptide-pulsed DC with anti-CD38 antibody can render an ICT-resistant “cold” tumor susceptible to immune rejection via a mechanism involving neutralization of regulatory T cells. We employed in-depth tumor analysis, including whole-exome sequencing, RNA-sequencing, and flow cytometry, to reveal the molecular mechanisms of resistance to ICT, and sought strategies to promote inflammatory/immunogenic pathway activation and inhibit immunosuppressive factors present in LLC1 tumors. ASB-XIV tumors are inflamed and are sensitive to ICT, while non-inflamed LLC1 tumors are resistant. The present study compared the ICT response of two murine lung cancer cell line models, ASB-XIV and LLC1. The absence of T cell infiltration and insufficient immune recognition may account for the primary resistance to immune checkpoint therapy. MicroRNA mediated gene regulation in human sarcomas gene expression profilesdeveloping novel diagnostic markers and identification of therapeutic targets in sarcomas and other cancers.įor more information, see Dr.Despite the substantial achievements to date, a significant proportion of patients still fail to benefit from immune-checkpoint therapies (ICT). Speaker invited by Ola Myklebost, Tumor Biologyīeckman JD, Chen C, Nguyen J, Thayanithy V, Subramanian S, Steer CJ, and Vercellotti GM. Regulation of Heme-Oxygenase-1 protein expression by miR-377 in combination with miR-217. miR-183 functions as a potential oncogene by targeting EGR1 and promoting tumor cell migration. Park C, Zeng Y, Zhang X, Subramanian S and Steer CJ. MicroRNAs identified in highly purified nuclei from HCT116 colon cancer cells. Sarver A, Phalak R, Thayanithy V, Subramanian S. S-MED: Sarcoma microRNA Expression Database. Subramanian S, Thayanithy V, West RB, Lee CH, Beck AH, Zhu S, Downs-Kelly E, Montgomery K, Goldblum JR, Hogendoorn PCW, Corless CL, Oliveira AM, Dry SM, Nielsen TO, Rubin BP, Fletcher JA, Fletcher CDM, van de Rijn M. Genome-wide transcriptome analyses reveals p53 inactivation mediated loss of miR-34a expression in malignant peripheral nerve sheath tumors. MicroRNAs in cardiovascular diseases: Biology and potential clinical applications. Wang L, Tang H, Thayanithy T, Subramanian S, Oberg AL, Cunningham JM, Cerhan JR, Steer CJ, Thibodeau SN. ![]() Gene networks and microRNAs implicated in aggressive prostate cancer. Lee CH, Subramanian S, Beck AH, Espinosa I, Senz J, Zhu S, Huntsman D, van de Rijn M, Gilks C. MicroRNA profiling of BRCA1/2 mutation-carrying and non-mutation carrying high-grade serous carcinomas of ovary. Sarver AL, French A, Borralho PM, Thayanithy V, Silverstein K, Morlan B, Oberg A, Cunningham J, Subramanian S, Wang L, Rodrigues C, Thibodeau SN, Steer CJ. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. ![]() Wang L, Oberg AL, Asmann YW, Sicotte H, McDonnell SK, Riska SM, Liu W, Steer CJ, Subramanian S, Cunningham JM, Cerhan JR and Thibodeau SN.
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