Data from Targeting STAT3 in Adoptively Transferred T Cells Promotes Their In Vivo Expansion and Antitumor Effects
Year: 2023
Type: other
Abstract: Adoptive cell therapy with engineered T cells to improve natural immune response and antitumor functions has shown promise for treating cancer. However, the requirement for extensive ex vivo manipulation of T cells and the immunosuppressive effects of the tumor microenvironment limit this therapeutic modality. In the present study, we investigated the possibility to circumvent these limitations by engineering Stat3 -deficient CD8+ T cells or by targeting Stat3 in the tumor microenvironment. We show that ablating Stat3in CD8+ T cells prior to their transfer allows their efficient tumor infiltration and robust proliferation, resulting in increased tumor antigen-specific T-cell activity and tumor growth inhibition. For potential clinical translation, we combined adoptive T-cell therapy with a Food and Drug Administration–approved tyrosine kinase inhibitor, sunitinib, in renal cell carcinoma and melanoma tumor models. Sunitinib inhibited Stat3 in dendritic cells and T cells and reduced conversion of transferred FoxP3− T cells to tumor-associated regulatory T cells while increasing transferred CD8+ T-cell infiltration and activation at the tumor site, leading to inhibition of primary tumor growth. These data show that adoptively transferred T cells can be expanded and activated in vivo either by engineering Stat3-silenced T cells or by targeting Stat3 systemically with small-molecule inhibitors. Cancer Res; 70(23); 9599–610. ©2010 AACR.
Authors: Maciej Kujawski, Chunyan Zhang, Andreas Herrmann, Karen Reckamp, Anna Scuto, Michael Jensen, Jiehui Deng, Stephen Forman, Robert Figlin, Hua Yu
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Funder: National Institutes of Health
OpenAlex ID: W4361243110