Natural killer and NK-Like T-cell activation in colorectal carcinoma patients treated with autologous tumor-derived heat shock protein 96

Cancer Res. 2005 May 1;65(9):3942-9. doi: 10.1158/0008-5472.CAN-04-3493.


Heat shock proteins (HSPs) are involved in the activation of both adaptive and innate immune systems. Here, we report that vaccination with autologous tumor-derived HSP96 of colorectal cancer patients, radically resected for liver metastases, induced a significant boost of natural killer (NK) activity detected as cytokine secretion and cytotoxicity in the presence of NK-sensitive targets. Increased NK activity was associated with a raise in CD3-CD56+ NK and/or CD3+CD56+ NK-like T cells, displaying enhanced expression of NKG2D and/or NKp46 receptors. Up-regulated expression of CD83 and CD40 and increased interleukin-12 release on stimulation were observed in CD14+ cells from post-HSP96 peripheral blood mononuclear cells, suggesting an indirect pathway of NK stimulation by HSP96-activated monocytes. Additionally, CD3-CD56+ and CD3+CD56+ lymphocytes were found to undergo functional and phenotypic activation on in vitro exposure to HSP96 even in the absence of monocytes, supporting a potential direct activity of HSP96 on these cell subsets. This evidence was confirmed by the specific binding of FITC-conjugated HSP96 to a subset of both CD3-CD56+ and CD3+CD56+ cells in peripheral blood mononuclear cells from colorectal cancer patients. Altogether, these findings identify the activation of the NK compartment as an additional immunologic effect of autologous tumor-derived HSP96 administration in cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / therapy
  • Disease-Free Survival
  • Heat-Shock Proteins / immunology*
  • Heat-Shock Proteins / therapeutic use
  • Humans
  • Immunotherapy, Active / methods
  • Killer Cells, Natural / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation
  • T-Lymphocytes / immunology*


  • Cancer Vaccines
  • Heat-Shock Proteins
  • vitespin