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

Academic Article

Abstract

  • 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.
  • Digital Object Identifier (doi)

    Author List

  • McCaw TR; Li M; Starenki D; Cooper SJ; Liu M; Meza-Perez S; Arend RC; Buchsbaum DJ; Forero A; Randall TD
  • Start Page

  • 175
  • End Page

  • 188
  • Volume

  • 68
  • Issue

  • 2