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.
Natural killer and NK-Like T-cell activation in colorectal carcinoma patients treated with autologous tumor-derived heat shock protein 96 / L. Pilla, P. Squarcina, J. Coppa, V. Mazzaferro, V. Huber, D. Pende, C. Maccalli, G. Sovena, L. Mariani, C. Castelli, G. Parmiani, L. Rivoltini. - In: CANCER RESEARCH. - ISSN 0008-5472. - 65:9(2005), pp. 3942-3949.
|Titolo:||Natural killer and NK-Like T-cell activation in colorectal carcinoma patients treated with autologous tumor-derived heat shock protein 96|
|Parole Chiave:||shock-protein GP96; toll-like receptor; dendritic cells; adaptive immunity; melanoma patients; cancer; NKG2D; cytotoxicity; induction; peptide|
|Settore Scientifico Disciplinare:||Settore MED/18 - Chirurgia Generale|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1158/0008-5472.CAN-04-3493|
|Appare nelle tipologie:||01 - Articolo su periodico|