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Data from Amplifying TLR-MyD88 Signals within Tumor-Specific T Cells Enhances Antitumor Activity to Suboptimal Levels of Weakly Immunogenic Tumor Antigens
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Data from Amplifying TLR-MyD88 Signals within Tumor-Specific T Cells Enhances Antitumor Activity to Suboptimal Levels of Weakly Immunogenic Tumor Antigens
Data from Amplifying TLR-MyD88 Signals within Tumor-Specific T Cells Enhances Antitumor Activity to Suboptimal Levels of Weakly Immunogenic Tumor Antigens
DG
Degui Geng
Degui Geng
LZ
Liqin Zheng
Liqin Zheng
RS
Ratika Srivastava
Ratika Srivastava
CV
Cruz Velasco-Gonzalez
Cruz Velasco-Gonzalez
AR
Adam Riker
Adam Riker
SM
Svetomir N. Markovic
Svetomir N. Markovic
ED
Eduardo Davila
Eduardo Davila
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30 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/0008-5472.c.6500703
Abstract
The efficacy of T cell–based immunotherapy to treat cancer patients remains a challenge partly because of the weak activity toward subdominant tumor antigens (TAg) and to tumors expressing suboptimal TAg levels. Recent reports indicate that Toll-like receptor (TLR) stimulation on T cells can lower the activation threshold. In this study, we examined the antitumor activity and survival of TLR2-MyD88–stimulated CD8 T cells derived from melanoma patients and T-cell receptor transgenic pmel mice. TLR2-stimulated pmel CD8 T cells, but not TLR2−/−pmel or MyD88−/−pmel T cells, responded to significantly lower TAg levels and resulted in increased production of effector molecules and cytotoxicity. Wild-type or MyD88−/− mice treated with TLR2 ligand and pmel T cells, but not TLR2−/−pmel or MyD88−/−pmel T cells, showed tumor regression of an established melanoma tumor. Overexpressing TLR2 in TAg-specific T cells eradicated tumors; four times fewer cells were needed to generate antitumor responses. The enhanced antitumor activity of TLR2-MyD88–stimulated T cells was associated with increased effector function but perhaps more importantly with improved survival of T cells. Activating TLR-MyD88 signals in patient-derived T cells also reduced the activation threshold to several weakly immunogenic TAgs, resulting in increased cytokine production, expansion, and cytotoxicity. These data highlight a previously unappreciated role for activating TLR-MyD88 signals in tumor-reactive T lymphocytes. Cancer Res; 70(19); 7442–54. ©2010 AACR.
Keywords
ANTIGENS
MYD88
ENHANCED ANTITUMOR ACTIVITY
EFFICACY
TAG
WEAKLY IMMUNOGENIC
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