American Association for Cancer Research
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Figure S5 from A Synthetic CD8α:MyD88 Coreceptor Enhances CD8+ T-cell Responses to Weakly Immunogenic and Lowly Expressed Tumor Antigens

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posted on 2023-03-31, 01:05 authored by Sabina Kaczanowska, Ann Mary Joseph, Jitao Guo, Alexander K Tsai, Jackline Joy Lasola, Kenisha Younger, Yuji Zhang, Cruz Velasco Gonzales, Eduardo Davila

These data demonstrate that a single injection of CD8a:MyD88 T cells delay tumor progression and can prolong mouse survival.


University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center

VA Merit Award

National Institute of Allergy and Infectious Diseases



T cell–based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T-cell efficacy, including suboptimal T-cell receptor (TCR) activation and an immunosuppressive tumor environment. Here, we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8+ T-cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88–engineered T cells exhibited increased proliferation and expression of effector and costimulatory molecules in a tumor antigen–dependent manner. These effects were accompanied by elevated activation of TCR and Toll-like receptor signaling-related proteins. CD8α:MyD88–expressing T cells improved antitumor responses in mice. Enhanced antitumor activity was associated with a unique tumor cytokine/chemokine signature, improved T-cell infiltration, reduced markers of T-cell exhaustion, elevated levels of proteins associated with antigen presentation, and fewer macrophages with an immunosuppressive phenotype in tumors. Given these observations, CD8α:MyD88 represents a unique and versatile approach to help overcome immunosuppression and enhance T-cell responses to tumor antigens. Cancer Res; 77(24); 7049–58. ©2017 AACR.