The expression of MHC class II molecules on murine breast tumors delays T-cell exhaustion, expands the T-cell repertoire, and slows tumor growth.

Autor: McCaw, Tyler R., Li, Mei, Starenki, Dmytro, Cooper, Sara J., Liu, Mingyong, Meza-Perez, Selene, Arend, Rebecca C., Buchsbaum, Donald J., Forero, Andres, Randall, Troy D.
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Zdroj: Cancer Immunology, Immunotherapy; Feb2019, Vol. 68 Issue 2, p175-188, 14p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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