Person:
Dowlatshahi, Mitra

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Dowlatshahi

First Name

Mitra

Name

Dowlatshahi, Mitra
Author's Publications: search.filters.isAuthorOfPublication.ec7175e8-a434-42ab-a374-037d041de48a

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Tumor-specific T cells in human Merkel cell carcinomas: a possible role for Tregs and T cell exhaustion in reducing T cell responses
    (2013) Dowlatshahi, Mitra; Huang, Victor; Gehad, Ahmed; Jiang, Ying; Calarese, Adam; Teague, Jessica E.; Dorosario, Andrew; Cheng, Jingwei; Nghiem, Paul; Schanbacher, Carl; Thakuria, Manisha; Schmults, Chrysalyne; Wang, Linda C.; Clark, Rachael
    Merkel cell carcinomas (MCC) are rare but highly malignant skin cancers associated with a novel polyomavirus. MCC tumors were infiltrated by T cells, including effector, central memory and regulatory T cells. Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T cell activation, proliferation, enhanced cytokine production and loss of viable tumor cells from cultures. Expanded tumor-infiltrating lymphocytes showed TCR repertoire skewing and upregulation of CD137. MCC tumors implanted into immunodeficient mice failed to grow unless human T cells in the tumor grafts were depleted with denileukin diftitox, suggesting tumor-specific T cells capable of controlling tumor growth were present in MCC. Both CD4+ and CD8+ FOXP3+ regulatory T cells were frequent in MCC. 50% of non-activated T cells in MCC expressed PD-1, a marker of T-cell exhaustion, and PD-L1 and PD-L2 were expressed by a subset of tumor dendritic cells and macrophages. In summary, we observed tumor-specific T cells with suppressed activity in MCC tumors. Agents that stimulate T cell activity, block Treg function or inhibit PD-1 signaling may be effective in the treatment of this highly malignant skin cancer.
  • No Thumbnail Available
    Publication
    Suppressed Activity of Tumor-Specific T Cells in Human Merkel Cell Carcinomas
    (2017-05-12) Dowlatshahi, Mitra
    Merkel cell carcinomas (MCC) are rare but highly malignant skin cancers associated with a novel polyomavirus. We studied T cells in MCC to determine how these virally mediated tumors evade immune responses. MCC tumors were infiltrated by T cells, including effector, central memory and increased numbers of CD4 and CD8 FOXP3+ regulatory T cells. Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T cell activation, proliferation, enhanced cytokine production and loss of viable tumor cells from cultures. Expanded tumor-infiltrating lymphocytes showed TCR repertoire skewing and upregulation of CD137. MCC tumors implanted into immunodeficient NOD/SCID/IL2 receptor g chainnull mice failed to grow unless human T cells in the tumor grafts were depleted with denileukin diftitox, suggesting tumor-specific T cells capable of controlling tumor growth were present in MCC. 50% of non-activated T cells in MCC expressed PD-1, a marker of T cell exhaustion, and PD-L1 and PD-L2 were expressed by a subset of tumor dendritic cells and macrophages. In summary, we observed tumor-specific T cells with suppressed activity in MCC tumors. Agents that stimulate T cell activity, block Treg function or inhibit PD-1 signaling may be effective in the treatment of this highly malignant skin cancer.