Jul 27, 2007

Mobilizing the low-avidity T cell repertoire to kill tumors

Seminars in Cancer Biology
Rachel H McMahan, Jill E Slansky

Abstract

Optimally, T cells destroy infected and transformed cells of the host. To be effective the T cell repertoire must have a sufficiently diverse number of T cell receptors (TCRs) to recognize the abundance of foreign and tumor antigens presented by MHC molecules. The T cell repertoire must also not be reactive toward self-antigens on healthy cells to prevent autoimmunity. Unlike antigens derived from pathogens, most tumor-associated antigens (TAA) are also self-antigens. Therefore, central and peripheral tolerance mechanisms delete or inhibit tumor-reactive T cells. Although there are T cells within the peripheral repertoire that recognize TAA, these T cells are not sufficient to prevent growth of clinically relevant tumors. We will discuss how this dysfunction results, in part, from the low functional avidity of T cells for tumor, or antigen presenting cells (APC) displaying TAA. We discuss the limitations of these low-avidity tumor-reactive T cells and review current immunotherapies aimed at enhancing the avidity and antitumor activity of the tumor-specific T cell repertoire.

  • References100
  • Citations23

Mentioned in this Paper

Pathologic Cytolysis
CD80 Antigens
ErbB-2 Receptor
Antigens, Differentiation
Tumor Cells, Uncertain Whether Benign or Malignant
Immune Response
ITGB2 wt Allele
Biochemical Pathway
Immune System
Melanocyte

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.