Coexisting Alterations of MHC Class I Antigen Presentation and IFNg Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy

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

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Coexisting Alterations of MHC Class I Antigen Presentation and IFNg Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy. / Nielsen, Morten; Presti, Mario; Sztupinszki, Zsofia; Jensen, Agnete Witness Præst; Draghi, Arianna; Chamberlain, Christopher Aled; Schina, Aimilia; Yde, Christina Westmose; Wojcik, John; Szallasi, Zoltan; Crowther, Michael Douglas; Svane, Inge Marie; Donia, Marco.

In: Cancer Immunology Research, Vol. 10, No. 10, 2022, p. 1254-1262.

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

Harvard

Nielsen, M, Presti, M, Sztupinszki, Z, Jensen, AWP, Draghi, A, Chamberlain, CA, Schina, A, Yde, CW, Wojcik, J, Szallasi, Z, Crowther, MD, Svane, IM & Donia, M 2022, 'Coexisting Alterations of MHC Class I Antigen Presentation and IFNg Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy', Cancer Immunology Research, vol. 10, no. 10, pp. 1254-1262. https://doi.org/10.1158/2326-6066.CIR-22-0326

APA

Nielsen, M., Presti, M., Sztupinszki, Z., Jensen, A. W. P., Draghi, A., Chamberlain, C. A., Schina, A., Yde, C. W., Wojcik, J., Szallasi, Z., Crowther, M. D., Svane, I. M., & Donia, M. (2022). Coexisting Alterations of MHC Class I Antigen Presentation and IFNg Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy. Cancer Immunology Research, 10(10), 1254-1262. https://doi.org/10.1158/2326-6066.CIR-22-0326

Vancouver

Nielsen M, Presti M, Sztupinszki Z, Jensen AWP, Draghi A, Chamberlain CA et al. Coexisting Alterations of MHC Class I Antigen Presentation and IFNg Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy. Cancer Immunology Research. 2022;10(10):1254-1262. https://doi.org/10.1158/2326-6066.CIR-22-0326

Author

Nielsen, Morten ; Presti, Mario ; Sztupinszki, Zsofia ; Jensen, Agnete Witness Præst ; Draghi, Arianna ; Chamberlain, Christopher Aled ; Schina, Aimilia ; Yde, Christina Westmose ; Wojcik, John ; Szallasi, Zoltan ; Crowther, Michael Douglas ; Svane, Inge Marie ; Donia, Marco. / Coexisting Alterations of MHC Class I Antigen Presentation and IFNg Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy. In: Cancer Immunology Research. 2022 ; Vol. 10, No. 10. pp. 1254-1262.

Bibtex

@article{1da1c4029a2c4fc79627d80615a58e8e,
title = "Coexisting Alterations of MHC Class I Antigen Presentation and IFNg Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy",
abstract = "Responses to immunotherapy can be very durable but acquired resistance leading to tumor progression often occurs. We investigated a patient with melanoma resistant to anti-programmed death 1 (anti-PD-1) who participated in the CA224-020 clinical trial (NCT01968109) and had further progression after an initial objective response to anti-PD-1 plus anti-lymphocyte activation gene 3. We found consecutive acquisition of beta-2 microglobulin (B2M) loss and impaired Janus kinase 1 (JAK1) signaling that coexisted in progressing tumor cells. Functional analyses revealed a pan T-cell immune escape phenotype, where distinct alterations mediated independent immune resistance to tumor killing by autologous CD8+ tumor-infiltrating lymphocytes (TIL; B2M loss) and CD4+ TILs (impaired JAK1 signaling). These findings shed light on the complexity of acquired resistance to immunotherapy in the post anti-PD-1 setting, indicating that coexisting altered pathways can lead to pan T-cell immune escape. ",
author = "Morten Nielsen and Mario Presti and Zsofia Sztupinszki and Jensen, {Agnete Witness Pr{\ae}st} and Arianna Draghi and Chamberlain, {Christopher Aled} and Aimilia Schina and Yde, {Christina Westmose} and John Wojcik and Zoltan Szallasi and Crowther, {Michael Douglas} and Svane, {Inge Marie} and Marco Donia",
note = "Publisher Copyright: {\textcopyright} 2022 American Association for Cancer Research.",
year = "2022",
doi = "10.1158/2326-6066.CIR-22-0326",
language = "English",
volume = "10",
pages = "1254--1262",
journal = "Cancer Immunology Research",
issn = "2326-6066",
publisher = "American Association for Cancer Research",
number = "10",

}

RIS

TY - JOUR

T1 - Coexisting Alterations of MHC Class I Antigen Presentation and IFNg Signaling Mediate Acquired Resistance of Melanoma to Post-PD-1 Immunotherapy

AU - Nielsen, Morten

AU - Presti, Mario

AU - Sztupinszki, Zsofia

AU - Jensen, Agnete Witness Præst

AU - Draghi, Arianna

AU - Chamberlain, Christopher Aled

AU - Schina, Aimilia

AU - Yde, Christina Westmose

AU - Wojcik, John

AU - Szallasi, Zoltan

AU - Crowther, Michael Douglas

AU - Svane, Inge Marie

AU - Donia, Marco

N1 - Publisher Copyright: © 2022 American Association for Cancer Research.

PY - 2022

Y1 - 2022

N2 - Responses to immunotherapy can be very durable but acquired resistance leading to tumor progression often occurs. We investigated a patient with melanoma resistant to anti-programmed death 1 (anti-PD-1) who participated in the CA224-020 clinical trial (NCT01968109) and had further progression after an initial objective response to anti-PD-1 plus anti-lymphocyte activation gene 3. We found consecutive acquisition of beta-2 microglobulin (B2M) loss and impaired Janus kinase 1 (JAK1) signaling that coexisted in progressing tumor cells. Functional analyses revealed a pan T-cell immune escape phenotype, where distinct alterations mediated independent immune resistance to tumor killing by autologous CD8+ tumor-infiltrating lymphocytes (TIL; B2M loss) and CD4+ TILs (impaired JAK1 signaling). These findings shed light on the complexity of acquired resistance to immunotherapy in the post anti-PD-1 setting, indicating that coexisting altered pathways can lead to pan T-cell immune escape.

AB - Responses to immunotherapy can be very durable but acquired resistance leading to tumor progression often occurs. We investigated a patient with melanoma resistant to anti-programmed death 1 (anti-PD-1) who participated in the CA224-020 clinical trial (NCT01968109) and had further progression after an initial objective response to anti-PD-1 plus anti-lymphocyte activation gene 3. We found consecutive acquisition of beta-2 microglobulin (B2M) loss and impaired Janus kinase 1 (JAK1) signaling that coexisted in progressing tumor cells. Functional analyses revealed a pan T-cell immune escape phenotype, where distinct alterations mediated independent immune resistance to tumor killing by autologous CD8+ tumor-infiltrating lymphocytes (TIL; B2M loss) and CD4+ TILs (impaired JAK1 signaling). These findings shed light on the complexity of acquired resistance to immunotherapy in the post anti-PD-1 setting, indicating that coexisting altered pathways can lead to pan T-cell immune escape.

U2 - 10.1158/2326-6066.CIR-22-0326

DO - 10.1158/2326-6066.CIR-22-0326

M3 - Journal article

C2 - 35969233

AN - SCOPUS:85142718098

VL - 10

SP - 1254

EP - 1262

JO - Cancer Immunology Research

JF - Cancer Immunology Research

SN - 2326-6066

IS - 10

ER -

ID: 340412557