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

Lorenzo Pilla, Paola Squarcina, Jorgelina Coppa, Vincenzo Mazzaferro, Veronica Huber, Daniela Pende, Cristina Maccalli, Gloria Sovena, Luigi Mariani, Chiara Castelli, Giorgio Parmiani, Licia Rivoltini

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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.

Original languageEnglish
Pages (from-to)3942-3949
Number of pages8
JournalCancer Research
Volume65
Issue number9
DOIs
Publication statusPublished - 1 May 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pilla, L., Squarcina, P., Coppa, J., Mazzaferro, V., Huber, V., Pende, D., Maccalli, C., Sovena, G., Mariani, L., Castelli, C., Parmiani, G., & Rivoltini, L. (2005). Natural killer and NK-like T-cell activation in colorectal carcinoma patients treated with autologous tumor-derived heat shock protein 96. Cancer Research, 65(9), 3942-3949. https://doi.org/10.1158/0008-5472.CAN-04-3493