Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma

Neoantigen-reactive CD8⁺ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Neoantigen-reactive CD8⁺ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma. / Kristensen, Nikolaj Pagh; Heeke, Christina; Tvingsholm, Siri A.; Borch, Annie; Draghi, Arianna; Crowther, Michael D.; Carri, Ibel; Munk, Kamilla K.; Holm, Jeppe Sejerø; Bjerregaard, Anne Mette; Bentzen, Amalie Kai; Marquard, Andrea M.; Szallasi, Zoltan; McGranahan, Nicholas; Andersen, Rikke; Nielsen, Morten; Jönsson, Göran B.; Donia, Marco; Svane, Inge Marie; Hadrup, Sine Reker.

I: Journal of Clinical Investigation, Bind 132, Nr. 2, 150535, 2022, s. 1-16.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Kristensen, NP, Heeke, C, Tvingsholm, SA, Borch, A, Draghi, A, Crowther, MD, Carri, I, Munk, KK, Holm, JS, Bjerregaard, AM, Bentzen, AK, Marquard, AM, Szallasi, Z, McGranahan, N, Andersen, R, Nielsen, M, Jönsson, GB, Donia, M, Svane, IM & Hadrup, SR 2022, 'Neoantigen-reactive CD8⁺ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma', Journal of Clinical Investigation, bind 132, nr. 2, 150535, s. 1-16. https://doi.org/10.1172/JCI150535

APA

Kristensen, N. P., Heeke, C., Tvingsholm, S. A., Borch, A., Draghi, A., Crowther, M. D., Carri, I., Munk, K. K., Holm, J. S., Bjerregaard, A. M., Bentzen, A. K., Marquard, A. M., Szallasi, Z., McGranahan, N., Andersen, R., Nielsen, M., Jönsson, G. B., Donia, M., Svane, I. M., & Hadrup, S. R. (2022). Neoantigen-reactive CD8⁺ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma. Journal of Clinical Investigation, 132(2), 1-16. [150535]. https://doi.org/10.1172/JCI150535

Vancouver

Kristensen NP, Heeke C, Tvingsholm SA, Borch A, Draghi A, Crowther MD o.a. Neoantigen-reactive CD8⁺ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma. Journal of Clinical Investigation. 2022;132(2):1-16. 150535. https://doi.org/10.1172/JCI150535

Author

Kristensen, Nikolaj Pagh ; Heeke, Christina ; Tvingsholm, Siri A. ; Borch, Annie ; Draghi, Arianna ; Crowther, Michael D. ; Carri, Ibel ; Munk, Kamilla K. ; Holm, Jeppe Sejerø ; Bjerregaard, Anne Mette ; Bentzen, Amalie Kai ; Marquard, Andrea M. ; Szallasi, Zoltan ; McGranahan, Nicholas ; Andersen, Rikke ; Nielsen, Morten ; Jönsson, Göran B. ; Donia, Marco ; Svane, Inge Marie ; Hadrup, Sine Reker. / Neoantigen-reactive CD8⁺ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma. I: Journal of Clinical Investigation. 2022 ; Bind 132, Nr. 2. s. 1-16.

Bibtex

@article{d470c79e33d1455cb941e0b23f2e3cbf,

title = "Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma",

abstract = "BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells. FUNDING. NEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation.",

author = "Kristensen, {Nikolaj Pagh} and Christina Heeke and Tvingsholm, {Siri A.} and Annie Borch and Arianna Draghi and Crowther, {Michael D.} and Ibel Carri and Munk, {Kamilla K.} and Holm, {Jeppe Sejer{\o}} and Bjerregaard, {Anne Mette} and Bentzen, {Amalie Kai} and Marquard, {Andrea M.} and Zoltan Szallasi and Nicholas McGranahan and Rikke Andersen and Morten Nielsen and J{\"o}nsson, {G{\"o}ran B.} and Marco Donia and Svane, {Inge Marie} and Hadrup, {Sine Reker}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2022, Kristensen et al.",

year = "2022",

doi = "10.1172/JCI150535",

language = "English",

volume = "132",

pages = "1--16",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

number = "2",

}

RIS

TY - JOUR

T1 - Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma

AU - Kristensen, Nikolaj Pagh

AU - Heeke, Christina

AU - Tvingsholm, Siri A.

AU - Borch, Annie

AU - Draghi, Arianna

AU - Crowther, Michael D.

AU - Carri, Ibel

AU - Munk, Kamilla K.

AU - Holm, Jeppe Sejerø

AU - Bjerregaard, Anne Mette

AU - Bentzen, Amalie Kai

AU - Marquard, Andrea M.

AU - Szallasi, Zoltan

AU - McGranahan, Nicholas

AU - Andersen, Rikke

AU - Nielsen, Morten

AU - Jönsson, Göran B.

AU - Donia, Marco

AU - Svane, Inge Marie

AU - Hadrup, Sine Reker

PY - 2022

Y1 - 2022

N2 - BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells. FUNDING. NEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation.

AB - BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells. FUNDING. NEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation.

UR - http://www.scopus.com/inward/record.url?scp=85123651400&partnerID=8YFLogxK

U2 - 10.1172/JCI150535

DO - 10.1172/JCI150535

M3 - Journal article

C2 - 34813506

AN - SCOPUS:85123651400

VL - 132

SP - 1

EP - 16

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 2

M1 - 150535

ER -

ID: 321468445