Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 68, Issue 2, Pages 175-188Publisher
SPRINGER
DOI: 10.1007/s00262-018-2262-5
Keywords
Breast cancer; MHC class II; T-cell exhaustion; TCR repertoire
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Funding
- University of Alabama at Birmingham Comprehensive Cancer Center [P30 CA013148]
- National Institutes of Health [CA216234]
- Breast Cancer Research Foundation of Alabama
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The expression of MHC class II molecules (MHCII) on tumor cells correlates with survival and responsiveness to immunotherapy. However, the mechanisms underlying these observations are poorly defined. Using a murine breast tumor line, we showed that MHCII-expressing tumors grew more slowly than controls and recruited more functional CD4(+) and CD8(+) T cells. In addition, MHCII-expressing tumors contained more TCR clonotypes expanded to a larger degree than control tumors. Functional CD8(+) T cells in tumors depended on CD4(+) T cells. However, both CD4(+) and CD8(+) T cells eventually became exhausted, even in MHCII-expressing tumors. Treatment with anti-CTLA4, but not anti-PD-1 or anti-TIM-3, promoted complete eradication of MHCII-expressing tumors. These results suggest tumor cell expression of MHCII facilitates the local activation of CD4(+) T cells, indirectly helps the activation and expansion of CD8(+) T cells, and, in combination with the appropriate checkpoint inhibitor, promotes tumor regression.
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