In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients

I. J.M. De Vries; M. R. Bernsen; W. L. Van Geloof; N. M. Scharenborg; W. J. Lesterhuis; P. D.M. Rombout; G. N.P. Van Muijen; C. G. Figdor; C. J.A. Punt; D. J. Ruiter; G. J. Adema

doi:10.1007/s00262-007-0304-5

In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients

I. J.M. De Vries
, M. R. Bernsen
, W. L. Van Geloof
, N. M. Scharenborg
, W. J. Lesterhuis
, P. D.M. Rombout
, G. N.P. Van Muijen
, C. G. Figdor
, C. J.A. Punt
, D. J. Ruiter
, G. J. Adema^*

^*Corresponding author for this work

Radboud Institute for Molecular Life Sciences - RIMLS
Radboud University Medical Center

Research output: Contribution to journal › Article › Academic › peer-review

24 Citations (Scopus)

Abstract

Application of tetrameric MHC class I-peptide complexes has significantly improved the monitoring of antigen-specific T cell immune responses in mouse models as well as in clinical studies. Especially MHC class I tetramer analysis of tumor-specific T cells in suspension or on thick vibratome sections from viable tissue has been proven extremely useful. Using the well-characterized mouse tyrosinase-related-protein-2 specific cytotoxic T cell (CTL) clone LP9, we now developed a method that allows for specific identification of T cells with MHC class I tetramers in 8 μm thick, chemically fixed cryosections. The protocol was validated in a murine influenza virus-infection model. Moreover, analysis of delayed type hypersensitivity (DTH) skin biopsies from melanoma patients vaccinated with peptide-loaded mature dendritic cells, revealed the presence and location of anti-tumor CTLs. The specificity of the CTLs detected in situ correlated with both the DTH challenge specificity and reactivity of cell suspensions derived from the same biopsies. Collectively, our data demonstrate that in situ MHC class I tetramer staining provides a valuable tool to reveal the presence and anatomical location of specific CTLs in frozen tissue following immune-based treatment strategies in cancer patients.

Original language	English
Pages (from-to)	1667-1676
Number of pages	10
Journal	Cancer Immunology, Immunotherapy
Volume	56
Issue number	10
DOIs	https://doi.org/10.1007/s00262-007-0304-5
Publication status	Published - Oct 2007
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgments We are grateful to F. A. Vyth-Dreese, K. Sche-pers H. Spits and T. Schumacher for providing precious material and for helpful suggestions. This study was supported by grants KUN 1995/1910, 1999/1950, 2000/2301, 2003/2893 and 2003/2917 from the Dutch Cancer Society and the TIL-foundation.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1007/s00262-007-0304-5

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De Vries, I. J. M., Bernsen, M. R., Van Geloof, W. L., Scharenborg, N. M., Lesterhuis, W. J., Rombout, P. D. M., Van Muijen, G. N. P., Figdor, C. G., Punt, C. J. A., Ruiter, D. J., & Adema, G. J. (2007). In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients. Cancer Immunology, Immunotherapy, 56(10), 1667-1676. https://doi.org/10.1007/s00262-007-0304-5

@article{1fce7d6d2a51467b9d0168989e52d1bf,

title = "In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients",

abstract = "Application of tetrameric MHC class I-peptide complexes has significantly improved the monitoring of antigen-specific T cell immune responses in mouse models as well as in clinical studies. Especially MHC class I tetramer analysis of tumor-specific T cells in suspension or on thick vibratome sections from viable tissue has been proven extremely useful. Using the well-characterized mouse tyrosinase-related-protein-2 specific cytotoxic T cell (CTL) clone LP9, we now developed a method that allows for specific identification of T cells with MHC class I tetramers in 8 μm thick, chemically fixed cryosections. The protocol was validated in a murine influenza virus-infection model. Moreover, analysis of delayed type hypersensitivity (DTH) skin biopsies from melanoma patients vaccinated with peptide-loaded mature dendritic cells, revealed the presence and location of anti-tumor CTLs. The specificity of the CTLs detected in situ correlated with both the DTH challenge specificity and reactivity of cell suspensions derived from the same biopsies. Collectively, our data demonstrate that in situ MHC class I tetramer staining provides a valuable tool to reveal the presence and anatomical location of specific CTLs in frozen tissue following immune-based treatment strategies in cancer patients.",

author = "\{De Vries\}, \{I. J.M.\} and Bernsen, \{M. R.\} and \{Van Geloof\}, \{W. L.\} and Scharenborg, \{N. M.\} and Lesterhuis, \{W. J.\} and Rombout, \{P. D.M.\} and \{Van Muijen\}, \{G. N.P.\} and Figdor, \{C. G.\} and Punt, \{C. J.A.\} and Ruiter, \{D. J.\} and Adema, \{G. J.\}",

note = "Funding Information: Acknowledgments We are grateful to F. A. Vyth-Dreese, K. Sche-pers H. Spits and T. Schumacher for providing precious material and for helpful suggestions. This study was supported by grants KUN 1995/1910, 1999/1950, 2000/2301, 2003/2893 and 2003/2917 from the Dutch Cancer Society and the TIL-foundation.",

year = "2007",

month = oct,

doi = "10.1007/s00262-007-0304-5",

language = "English",

volume = "56",

pages = "1667--1676",

journal = "Cancer Immunology, Immunotherapy",

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De Vries, IJM, Bernsen, MR, Van Geloof, WL, Scharenborg, NM, Lesterhuis, WJ, Rombout, PDM, Van Muijen, GNP, Figdor, CG, Punt, CJA, Ruiter, DJ & Adema, GJ 2007, 'In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients', Cancer Immunology, Immunotherapy, vol. 56, no. 10, pp. 1667-1676. https://doi.org/10.1007/s00262-007-0304-5

TY - JOUR

T1 - In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients

AU - De Vries, I. J.M.

AU - Bernsen, M. R.

AU - Van Geloof, W. L.

AU - Scharenborg, N. M.

AU - Lesterhuis, W. J.

AU - Rombout, P. D.M.

AU - Van Muijen, G. N.P.

AU - Figdor, C. G.

AU - Punt, C. J.A.

AU - Ruiter, D. J.

AU - Adema, G. J.

N1 - Funding Information: Acknowledgments We are grateful to F. A. Vyth-Dreese, K. Sche-pers H. Spits and T. Schumacher for providing precious material and for helpful suggestions. This study was supported by grants KUN 1995/1910, 1999/1950, 2000/2301, 2003/2893 and 2003/2917 from the Dutch Cancer Society and the TIL-foundation.

PY - 2007/10

Y1 - 2007/10

N2 - Application of tetrameric MHC class I-peptide complexes has significantly improved the monitoring of antigen-specific T cell immune responses in mouse models as well as in clinical studies. Especially MHC class I tetramer analysis of tumor-specific T cells in suspension or on thick vibratome sections from viable tissue has been proven extremely useful. Using the well-characterized mouse tyrosinase-related-protein-2 specific cytotoxic T cell (CTL) clone LP9, we now developed a method that allows for specific identification of T cells with MHC class I tetramers in 8 μm thick, chemically fixed cryosections. The protocol was validated in a murine influenza virus-infection model. Moreover, analysis of delayed type hypersensitivity (DTH) skin biopsies from melanoma patients vaccinated with peptide-loaded mature dendritic cells, revealed the presence and location of anti-tumor CTLs. The specificity of the CTLs detected in situ correlated with both the DTH challenge specificity and reactivity of cell suspensions derived from the same biopsies. Collectively, our data demonstrate that in situ MHC class I tetramer staining provides a valuable tool to reveal the presence and anatomical location of specific CTLs in frozen tissue following immune-based treatment strategies in cancer patients.

AB - Application of tetrameric MHC class I-peptide complexes has significantly improved the monitoring of antigen-specific T cell immune responses in mouse models as well as in clinical studies. Especially MHC class I tetramer analysis of tumor-specific T cells in suspension or on thick vibratome sections from viable tissue has been proven extremely useful. Using the well-characterized mouse tyrosinase-related-protein-2 specific cytotoxic T cell (CTL) clone LP9, we now developed a method that allows for specific identification of T cells with MHC class I tetramers in 8 μm thick, chemically fixed cryosections. The protocol was validated in a murine influenza virus-infection model. Moreover, analysis of delayed type hypersensitivity (DTH) skin biopsies from melanoma patients vaccinated with peptide-loaded mature dendritic cells, revealed the presence and location of anti-tumor CTLs. The specificity of the CTLs detected in situ correlated with both the DTH challenge specificity and reactivity of cell suspensions derived from the same biopsies. Collectively, our data demonstrate that in situ MHC class I tetramer staining provides a valuable tool to reveal the presence and anatomical location of specific CTLs in frozen tissue following immune-based treatment strategies in cancer patients.

UR - https://www.scopus.com/pages/publications/34447621081

U2 - 10.1007/s00262-007-0304-5

DO - 10.1007/s00262-007-0304-5

M3 - Article

C2 - 17440724

AN - SCOPUS:34447621081

SN - 0340-7004

VL - 56

SP - 1667

EP - 1676

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

IS - 10

ER -

In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients

Abstract

Bibliographical note

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