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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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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Natural Killer T-Cells
Colorectal Neoplasms
Neoplasms
Natural Cytotoxicity Triggering Receptor 1
Monocytes
Blood Cells
NK Cell Lectin-Like Receptor Subfamily K
Fluorescein-5-isothiocyanate
Interleukin-12
Heat-Shock Proteins
sarcoma glycoprotein gp96 rejection antigens
Immune System
Vaccination
Lymphocytes
Cytokines
Neoplasm Metastasis
Liver

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Natural killer and NK-like T-cell activation in colorectal carcinoma patients treated with autologous tumor-derived heat shock protein 96. / Pilla, Lorenzo; Squarcina, Paola; Coppa, Jorgelina; Mazzaferro, Vincenzo; Huber, Veronica; Pende, Daniela; Maccalli, Cristina; Sovena, Gloria; Mariani, Luigi; Castelli, Chiara; Parmiani, Giorgio; Rivoltini, Licia.

In: Cancer Research, Vol. 65, No. 9, 01.05.2005, p. 3942-3949.

Research output: Contribution to journalArticle

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, vol. 65, no. 9, pp. 3942-3949. https://doi.org/10.1158/0008-5472.CAN-04-3493
Pilla, Lorenzo ; Squarcina, Paola ; Coppa, Jorgelina ; Mazzaferro, Vincenzo ; Huber, Veronica ; Pende, Daniela ; Maccalli, Cristina ; Sovena, Gloria ; Mariani, Luigi ; Castelli, Chiara ; Parmiani, Giorgio ; Rivoltini, Licia. / Natural killer and NK-like T-cell activation in colorectal carcinoma patients treated with autologous tumor-derived heat shock protein 96. In: Cancer Research. 2005 ; Vol. 65, No. 9. pp. 3942-3949.
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