Our study indicates that tumor location affects immune response in CRC mouse models choosing the appropriate preclinical model is important when testing immunotherapy in CRC. Those differences resulted in heightened sensitivity to immune checkpoint blockade therapy in our endoscopy-guided orthotopic CRC model. The number of immune-stimulating cytokines, such as interleukin (IL)-2, IL-6, interferon (IFN)-gamma, and granzyme B, was also higher in tumors in our model, as compared with the subcutaneous model. When we compared immune system infiltration, we found that tumors in the subcutaneous model had fewer T cells, B cells, and natural killer (NK) cells, but more immunosuppressive myeloid cells in contrast, tumors in our orthotopic model had a higher number of tumor-infiltrating T cells, B cells, and NK cells, with fewer immunosuppressive myeloid cells. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. Received: MaAccepted: Published: June 09, 2017Įxisting preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Keywords: colorectal cancer, immune profiles, immunotherapy, mouse models of cancer, orthotopic models Starr 2 and Subbaya Subramanian 1, 3ġDepartment of Surgery, University of Minnesota Medical School, Minneapolis, MN, USAĢDepartment of Obstetrics and Gynecology and Women’s Health, University of Minnesota Medical School, Minneapolis, MN, USAģMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA 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.Xianda Zhao 1, Lihua Li 1, Timothy K. 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. EV Therapeutics is a pre-clinical stage biotechnology company comprised of passionate scientists, clinical and regulatory experts, and seasoned commercial leaders who are devoted to developing first-in-class immuno-therapies based on modified tumor extracellular vesicles (mTEVs) to significantly. MicroRNA profiling of BRCA1/2 mutation-carrying and non-mutation carrying high-grade serous carcinomas of ovary. Our Team: Passionate - Innovative - Disciplined. 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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