B7-H3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of antigen-specific CD8+ cytolytic T cells

J Immunol. 2004 Nov 1;173(9):5445-50. doi: 10.4049/jimmunol.173.9.5445.

Abstract

B7-H3 is a B7 family molecule with T cell costimulatory function in vitro. The in vivo role of B7-H3 in the stimulation of tumor immunity is unclear. We report here that expression of B7-H3 by transfection of the mouse P815 tumor line enhances its immunogenicity, leading to the regression of tumors and amplification of a tumor-specific CD8+ CTL response in syngeneic mice. Tumor cells engineered to express B7-H3 elicit a rapid clonal expansion of P1A tumor Ag-specific CD8+ CTL in lymphoid organs in vivo and acquire the ability to directly stimulate T cell growth, division, and development of cytolytic activity in vitro. Our results thus establish a role for B7-H3 in the costimulation of T cell immune responses in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / physiology*
  • Animals
  • B7 Antigens
  • B7-1 Antigen / genetics
  • B7-1 Antigen / physiology*
  • CHO Cells
  • Cell Division / immunology
  • Cell Line, Tumor
  • Clone Cells
  • Cricetinae
  • Cytotoxicity Tests, Immunologic
  • DNA, Complementary / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Lymphocyte Activation / immunology*
  • Mast-Cell Sarcoma / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Nude
  • Mice, Transgenic
  • T-Lymphocytes, Cytotoxic / cytology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection

Substances

  • Adjuvants, Immunologic
  • B7 Antigens
  • B7-1 Antigen
  • Cd276 protein, mouse
  • DNA, Complementary
  • Epitopes, T-Lymphocyte