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

Transfection with the human class II transcriptional activator (hCIITA) promotes MHCII expression on TS/A breast cancer cells. 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. Additionally, 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. To test whether local MHCII expression promoted T cell clonal expansion or accumulation, we harvested 12 control and 12 MHCII-expressing whole tumor samples and sequenced the CDR3 region of the TCRbeta chain to identify unique T cell clones.