Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNϒ, Following Recognition of Autologous Tumor-Antigens

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNϒ, Following Recognition of Autologous Tumor-Antigens. / Draghi, Arianna; Chamberlain, Christopher Aled; Khan, Shawez; Papp, Krisztian; Lauss, Martin; Soraggi, Samuele; Radic, Haja Dominike; Presti, Mario; Harbst, Katja; Gokuldass, Aishwarya; Kverneland, Anders; Nielsen, Morten; Westergaard, Marie Christine Wulff; Andersen, Mads Hald; Csabai, Istvan; Jönsson, Göran; Szallasi, Zoltan; Svane, Inge Marie; Donia, Marco.

In: Frontiers in Immunology, Vol. 12, 705422, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Draghi, A, Chamberlain, CA, Khan, S, Papp, K, Lauss, M, Soraggi, S, Radic, HD, Presti, M, Harbst, K, Gokuldass, A, Kverneland, A, Nielsen, M, Westergaard, MCW, Andersen, MH, Csabai, I, Jönsson, G, Szallasi, Z, Svane, IM & Donia, M 2021, 'Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNϒ, Following Recognition of Autologous Tumor-Antigens', Frontiers in Immunology, vol. 12, 705422. https://doi.org/10.3389/fimmu.2021.705422

APA

Draghi, A., Chamberlain, C. A., Khan, S., Papp, K., Lauss, M., Soraggi, S., Radic, H. D., Presti, M., Harbst, K., Gokuldass, A., Kverneland, A., Nielsen, M., Westergaard, M. C. W., Andersen, M. H., Csabai, I., Jönsson, G., Szallasi, Z., Svane, I. M., & Donia, M. (2021). Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNϒ, Following Recognition of Autologous Tumor-Antigens. Frontiers in Immunology, 12, [705422]. https://doi.org/10.3389/fimmu.2021.705422

Vancouver

Draghi A, Chamberlain CA, Khan S, Papp K, Lauss M, Soraggi S et al. Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNϒ, Following Recognition of Autologous Tumor-Antigens. Frontiers in Immunology. 2021;12. 705422. https://doi.org/10.3389/fimmu.2021.705422

Author

Draghi, Arianna ; Chamberlain, Christopher Aled ; Khan, Shawez ; Papp, Krisztian ; Lauss, Martin ; Soraggi, Samuele ; Radic, Haja Dominike ; Presti, Mario ; Harbst, Katja ; Gokuldass, Aishwarya ; Kverneland, Anders ; Nielsen, Morten ; Westergaard, Marie Christine Wulff ; Andersen, Mads Hald ; Csabai, Istvan ; Jönsson, Göran ; Szallasi, Zoltan ; Svane, Inge Marie ; Donia, Marco. / Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNϒ, Following Recognition of Autologous Tumor-Antigens. In: Frontiers in Immunology. 2021 ; Vol. 12.

Bibtex

@article{d20a86ca17fb49cab15310128b15a800,
title = "Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNϒ, Following Recognition of Autologous Tumor-Antigens",
abstract = "Detecting the entire repertoire of tumor-specific reactive tumor-infiltrating lymphocytes (TILs) is essential for investigating their immunological functions in the tumor microenvironment. Current in vitro assays identifying tumor-specific functional activation measure the upregulation of surface molecules, de novo production of antitumor cytokines, or mobilization of cytotoxic granules following recognition of tumor-antigens, yet there is no widely adopted standard method. Here we established an enhanced, yet simple, method for identifying simultaneously CD8+ and CD4+ tumor-specific reactive TILs in vitro, using a combination of widely known and available flow cytometry assays. By combining the detection of intracellular CD137 and de novo production of TNF and IFNγ after recognition of naturally-presented tumor antigens, we demonstrate that a larger fraction of tumor-specific and reactive CD8+ TILs can be detected in vitro compared to commonly used assays. This assay revealed multiple polyfunctionality-based clusters of both CD4+ and CD8+ tumor-specific reactive TILs. In situ, the combined detection of TNFRSF9, TNF, and IFNG identified most of the tumor-specific reactive TIL repertoire. In conclusion, we describe a straightforward method for efficient identification of the tumor-specific reactive TIL repertoire in vitro, which can be rapidly adopted in most cancer immunology laboratories.",
keywords = "CD137 (4-1BB), immune-monitoring, immune-responses to cancer, single-cell technologies, tumor-infiltrating lymphocytes (TILs), tumor-specific activation, tumor-specific reactivity",
author = "Arianna Draghi and Chamberlain, {Christopher Aled} and Shawez Khan and Krisztian Papp and Martin Lauss and Samuele Soraggi and Radic, {Haja Dominike} and Mario Presti and Katja Harbst and Aishwarya Gokuldass and Anders Kverneland and Morten Nielsen and Westergaard, {Marie Christine Wulff} and Andersen, {Mads Hald} and Istvan Csabai and G{\"o}ran J{\"o}nsson and Zoltan Szallasi and Svane, {Inge Marie} and Marco Donia",
note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Draghi, Chamberlain, Khan, Papp, Lauss, Soraggi, Radic, Presti, Harbst, Gokuldass, Kverneland, Nielsen, Westergaard, Andersen, Csabai, J{\"o}nsson, Szallasi, Svane and Donia.",
year = "2021",
doi = "10.3389/fimmu.2021.705422",
language = "English",
volume = "12",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Rapid Identification of the Tumor-Specific Reactive TIL Repertoire via Combined Detection of CD137, TNF, and IFNϒ, Following Recognition of Autologous Tumor-Antigens

AU - Draghi, Arianna

AU - Chamberlain, Christopher Aled

AU - Khan, Shawez

AU - Papp, Krisztian

AU - Lauss, Martin

AU - Soraggi, Samuele

AU - Radic, Haja Dominike

AU - Presti, Mario

AU - Harbst, Katja

AU - Gokuldass, Aishwarya

AU - Kverneland, Anders

AU - Nielsen, Morten

AU - Westergaard, Marie Christine Wulff

AU - Andersen, Mads Hald

AU - Csabai, Istvan

AU - Jönsson, Göran

AU - Szallasi, Zoltan

AU - Svane, Inge Marie

AU - Donia, Marco

N1 - Publisher Copyright: © Copyright © 2021 Draghi, Chamberlain, Khan, Papp, Lauss, Soraggi, Radic, Presti, Harbst, Gokuldass, Kverneland, Nielsen, Westergaard, Andersen, Csabai, Jönsson, Szallasi, Svane and Donia.

PY - 2021

Y1 - 2021

N2 - Detecting the entire repertoire of tumor-specific reactive tumor-infiltrating lymphocytes (TILs) is essential for investigating their immunological functions in the tumor microenvironment. Current in vitro assays identifying tumor-specific functional activation measure the upregulation of surface molecules, de novo production of antitumor cytokines, or mobilization of cytotoxic granules following recognition of tumor-antigens, yet there is no widely adopted standard method. Here we established an enhanced, yet simple, method for identifying simultaneously CD8+ and CD4+ tumor-specific reactive TILs in vitro, using a combination of widely known and available flow cytometry assays. By combining the detection of intracellular CD137 and de novo production of TNF and IFNγ after recognition of naturally-presented tumor antigens, we demonstrate that a larger fraction of tumor-specific and reactive CD8+ TILs can be detected in vitro compared to commonly used assays. This assay revealed multiple polyfunctionality-based clusters of both CD4+ and CD8+ tumor-specific reactive TILs. In situ, the combined detection of TNFRSF9, TNF, and IFNG identified most of the tumor-specific reactive TIL repertoire. In conclusion, we describe a straightforward method for efficient identification of the tumor-specific reactive TIL repertoire in vitro, which can be rapidly adopted in most cancer immunology laboratories.

AB - Detecting the entire repertoire of tumor-specific reactive tumor-infiltrating lymphocytes (TILs) is essential for investigating their immunological functions in the tumor microenvironment. Current in vitro assays identifying tumor-specific functional activation measure the upregulation of surface molecules, de novo production of antitumor cytokines, or mobilization of cytotoxic granules following recognition of tumor-antigens, yet there is no widely adopted standard method. Here we established an enhanced, yet simple, method for identifying simultaneously CD8+ and CD4+ tumor-specific reactive TILs in vitro, using a combination of widely known and available flow cytometry assays. By combining the detection of intracellular CD137 and de novo production of TNF and IFNγ after recognition of naturally-presented tumor antigens, we demonstrate that a larger fraction of tumor-specific and reactive CD8+ TILs can be detected in vitro compared to commonly used assays. This assay revealed multiple polyfunctionality-based clusters of both CD4+ and CD8+ tumor-specific reactive TILs. In situ, the combined detection of TNFRSF9, TNF, and IFNG identified most of the tumor-specific reactive TIL repertoire. In conclusion, we describe a straightforward method for efficient identification of the tumor-specific reactive TIL repertoire in vitro, which can be rapidly adopted in most cancer immunology laboratories.

KW - CD137 (4-1BB)

KW - immune-monitoring

KW - immune-responses to cancer

KW - single-cell technologies

KW - tumor-infiltrating lymphocytes (TILs)

KW - tumor-specific activation

KW - tumor-specific reactivity

U2 - 10.3389/fimmu.2021.705422

DO - 10.3389/fimmu.2021.705422

M3 - Journal article

C2 - 34707600

AN - SCOPUS:85117920197

VL - 12

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 705422

ER -

ID: 302067730