Mechanisms of tumor escape: Role of tumor microenvironment in inducing apoptosis of cytolytic effector cells

Alessandro Poggi, Maria Raffaella Zocchi

Research output: Contribution to journalArticlepeer-review

Abstract

Spontaneous tumors grow and kill the host unless therapy reduces their mass to a level where the immune system, it is thought, can control their growth and diffusion. Indeed, in many instances tumors can reappear, become resistant to therapy, and escape the host immune response. Many mechanisms of tumor escape operating in the tumor microenvironment have been proposed: 1) low or absent expression of molecules on tumor cells involved in tumor target cell recognition; 2) absence of co-stimulation leading to tolerization of T cells; 3) soluble factors secreted by tumor cells inhibiting T cell response; and 4) regulatory T cells, myeloid suppressor cells, and stromal cells may impair immune-cell responses to tumors. Furthermore, tumors can release soluble molecules such as HLA-I (sHLA-I). This, in turn, reduces T cell-mediated immune response and induces apoptosis of cytolytic effector cells such as natural killer and CD8+ T lymphocytes through the engagement of HLA-I receptors such as CD8 and/or activating isoforms of the inhibitory receptor superfamily. The release of soluble ligand for activating receptors, e.g. UL16 binding proteins and/or MHC class I-related proteins A and B, the natural ligands of NKG2D, may impair activation, effector cell-mediated recognition, and cytolysis of tumor cells. Furthermore, the elimination of anti-tumor effector cells may be achieved by induction of apoptosis consequent to triggering elicited via activating molecules, such as receptors responsible for natural cytotoxicity, upon their binding with ligands expressed on tumor cells.

Original languageEnglish
Pages (from-to)323-333
Number of pages11
JournalArchivum Immunologiae et Therapiae Experimentalis
Volume54
Issue number5
DOIs
Publication statusPublished - Oct 2006

Keywords

  • Apoptosis
  • Natural cytotoxicity receptor
  • NKG2D
  • Soluble HLA-I
  • Stromal cells
  • Tumor escape

ASJC Scopus subject areas

  • Immunology

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