- Browse by Subject
Browsing by Subject "T-cells"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item The PPARγ Agonist Rosiglitazone Suppresses Syngeneic Mouse SCC (Squamous Cell Carcinoma) Tumor Growth through an Immune-Mediated Mechanism(MDPI, 2019-06-11) Konger, Raymond L.; Derr-Yellin, Ethel; Ermatov, Nurmukambed; Ren, Lu; Sahu, Ravi P.; Pathology & Laboratory Medicine, IU School of MedicineRecent evidence suggests that PPARγ agonists may promote anti-tumor immunity. We show that immunogenic PDV cutaneous squamous cell carcinoma (CSCC) tumors are rejected when injected intradermally at a low cell number (1 × 106) into immune competent syngeneic hosts, but not immune deficient mice. At higher cell numbers (5 × 106 PDV cells), progressively growing tumors were established in 14 of 15 vehicle treated mice while treatment of mice with the PPARγ agonist rosiglitazone resulted in increased tumor rejection (5 of 14 tumors), a significant decrease in PDV tumor size, and a significant decrease in tumor cell Ki67 labeling. Rosiglitazone treatment had no effect on tumor rejection, tumor volume or PDV tumor cell proliferation in immune deficient NOD.CB17-PrkdcSCID/J mice. Rosiglitazone treatment also promoted an increase in tumor infiltrating CD3+ T-cells at both early and late time points. In contrast, rosiglitazone treatment had no significant effect on myeloid cells expressing either CD11b or Gr-1 but suppressed a late accumulation of myeloid cells expressing both CD11b and Gr-1, suggesting a potential role for CD11b+Gr-1+ myeloid cells in the late anti-tumor immune response. Overall, our data provides evidence that the PPARγ agonist rosiglitazone promotes immune-mediated anti-neoplastic activity against tumors derived from this immunogenic CSCC cell line.Item The stimulatory role of ICOS in the development of CD146+CCR5+ T cells co-expressing IFN-γ and IL-17 during graft-versus-host disease(2015) Liu, Liangyi; Paczesny, Sophie; Broxmeyer, Hal E.; Blum, Janice S.; Haneline, Laura S.; Carlesso, NadiaGraft-versus-host disease (GVHD) remains the major complication after allogeneic hematopoietic stem cell transplantation (HSCT), resulting from immunological attack on target organs such as gastrointestinal (GI) tract, liver and skin from donor allogeneic T cells. The most common treatment for GVHD is immunosuppressive drugs such as corticosteroids, which may result in many side effects including the loss of the beneficial graft-versus-leukemia (GVL) effect and increased infection rates. However, GVHD-specific drugs have yet to be implemented. Here we show that by targeting on a novel pathogenic CD4+ T cell subpopulation that our lab previously found in patients with GI GVHD, we can develop new avenues to treat GVHD. This novel population is characterized as CD146+CCR5+ T cells, co-expressing IL-17A and IFN-γ. We found that the inducible T-cell costimulator (ICOS), which has been reported to be important for human Th17 differentiation in vitro, is critical for the development of this nonconventional T Helper 1 (Th1*)-polarized CD146+CCR5+ conventional T cells (Tconvs) population. Furthermore, we found that ICOS can induce the generation of Th1*-polarized CD146+CCR5+ regulatory T cells (Tregs) population, lowering the frequencies of phenotypic markers of functional Tregs. Our data also showed that inhibiting the major transcriptional factor of Th17, RAR-related orphan receptor gamma t (RORγt), could prevent the development of CD146+CCR5+ Tconvs in vitro. Our results demonstrate how pathogenic CD146+CCR5+ T cells are induced through ICOS or RORγt, suggesting new targets for GVHD treatment. We anticipate our assay to be a starting point for the development of novel GVHD-specific drugs. For example, the treatments that focus on inhibiting RORγ would have fewer side effects than general immunosuppressive drugs that GVHD patients use today and inhibit GVHD while sparing the GVL effect. Furthermore, we expect the CD146+CCR5+ Tconvs and/or Tregs can be used as GVHD biomarkers. These biomarkers may guide preemptive treatments such as RORγt inhibitor.