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

Abstract

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.

• Authors: Lorenzo Pilla, Paola Squarcina, Jorgelina Coppa, Vincenzo Mazzaferro, Veronica Huber, Daniela Pende, Cristina Maccalli, Gloria Sovena, Luigi Mariani, Chiara Castelli, Giorgio Parmiani, Licia Rivoltini
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 9 Pg. 3942-9 (May 01 2005) ISSN: 0008-5472 [Print] United States
• PMID: 15867395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Heat-Shock Proteins
• vitespin

Topics

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