Τίτλος:
Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Spontaneous tumors frequently express antigens that can be recognized by the immune system but nevertheless manage to evade immune surveillance. To better understand the mechanism of evasion, we followed CD8 and CD4 T cells reacting against a subcutaneously growing tumor, modified to express influenza hemagglutinin (HA) as surrogate tumor antigen. Adoptive transfer of 8,000 antigen-specific CD8 T cells was sufficient to protect against challenge with 1×106 tumor cells, while larger numbers of T cells rejected established tumors. HA-specific CD4 T cells could not reject tumors on their own but helped rejection by CD8 T cells. Rejection of the tumor coincided with prolonged survival of expanded antigen-specific CD8 and CD4 T cells, while a failing anti-tumor response was accompanied by transient expansion followed by rapid elimination of antigen-specific T cells. Thus, a highly immunogenic tumor can evade immune surveillance because of an insufficient number of tumor-specific T cells and antigen overload, resulting in exhaustion of the immune response. In this scenario, adoptive immunotherapy rather than vaccination promises successful treatment.
Συγγραφείς:
Klein, L.
Trautman, L.
Psarras, S.
Schnell, S.
Siermann, A.
Liblau, R.
von Boehmer, H.
Khazaie, K.
Περιοδικό:
European Journal of Immunology
Λέξεις-κλειδιά:
CD4 antigen; CD8 antigen; Influenza virus hemagglutinin; tumor antigen; tumor marker, adoptive immunotherapy; adoptive transfer; animal cell; antigen expression; antigen recognition; antigen specificity; cell survival; cellular immunity; controlled study; helper cell; immune response; immunogenicity; immunoregulation; immunosurveillance; mouse; nonhuman; priority journal; review; subcutaneous tissue tumor; T lymphocyte; tumor cell; tumor growth; tumor rejection, Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Graft Rejection; Hemagglutinin Glycoproteins, Influenza Virus; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms, Experimental
DOI:
10.1002/eji.200323800
