Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy

Michael Friedrich; Simon Jasinski-Bergner; Maria Filothei Lazaridou; Karthikeyan Subbarayan; Chiara Massa; Sandy Tretbar; Anja Mueller; Diana Handke; Katharina Biehl; Jürgen Bukur; Marco Donia; Ofer Mandelboim; Barbara Seliger

doi:10.1007/s00262-019-02373-1

Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy

Michael Friedrich, Simon Jasinski-Bergner, Maria Filothei Lazaridou, Karthikeyan Subbarayan, Chiara Massa, Sandy Tretbar, Anja Mueller, Diana Handke, Katharina Biehl, Jürgen Bukur, Marco Donia, Ofer Mandelboim, Barbara Seliger^*

^*Corresponding author for this work

Department of Immunology and Cancer Research

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

52 Scopus citations

Abstract

Immunotherapy aims to activate the immune system to fight cancer in a very specific and targeted manner. Despite the success of different immunotherapeutic strategies, in particular antibodies directed against checkpoints as well as adoptive T-cell therapy, the response of patients is limited in different types of cancers. This attributes to escape of the tumor from immune surveillance and development of acquired resistances during therapy. In this review, the different evasion and resistance mechanisms that limit the efficacy of immunotherapies targeting tumor-associated antigens presented by major histocompatibility complex molecules on the surface of the malignant cells are summarized. Overcoming these escape mechanisms is a great challenge, but might lead to a better clinical outcome of patients and is therefore currently a major focus of research.

Original language	American English
Pages (from-to)	1689-1700
Number of pages	12
Journal	Cancer Immunology, Immunotherapy
Volume	68
Issue number	10
DOIs	https://doi.org/10.1007/s00262-019-02373-1
State	Published - 1 Oct 2019

Bibliographical note

Funding Information:
This work was funded by the German Research Foundation (DFG; SE 581/22-1 and RTG, 1591/2-B4), the German Israeli Foundation for Scientific Research and Development (GIF; I-37-414.11-2016), and the Mildred Scheel Foundation. Acknowledgements

Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

Immune escape
Immunotherapy
MHC
Resistance
TIMO XIV
Tumor

UN SDGs

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

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10.1007/s00262-019-02373-1

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Friedrich, M., Jasinski-Bergner, S., Lazaridou, M. F., Subbarayan, K., Massa, C., Tretbar, S., Mueller, A., Handke, D., Biehl, K., Bukur, J., Donia, M., Mandelboim, O., & Seliger, B. (2019). Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy. Cancer Immunology, Immunotherapy, 68(10), 1689-1700. https://doi.org/10.1007/s00262-019-02373-1

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abstract = "Immunotherapy aims to activate the immune system to fight cancer in a very specific and targeted manner. Despite the success of different immunotherapeutic strategies, in particular antibodies directed against checkpoints as well as adoptive T-cell therapy, the response of patients is limited in different types of cancers. This attributes to escape of the tumor from immune surveillance and development of acquired resistances during therapy. In this review, the different evasion and resistance mechanisms that limit the efficacy of immunotherapies targeting tumor-associated antigens presented by major histocompatibility complex molecules on the surface of the malignant cells are summarized. Overcoming these escape mechanisms is a great challenge, but might lead to a better clinical outcome of patients and is therefore currently a major focus of research.",

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note = "Funding Information: This work was funded by the German Research Foundation (DFG; SE 581/22-1 and RTG, 1591/2-B4), the German Israeli Foundation for Scientific Research and Development (GIF; I-37-414.11-2016), and the Mildred Scheel Foundation. Acknowledgements Publisher Copyright: {\textcopyright} 2019, Springer-Verlag GmbH Germany, part of Springer Nature.",

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Friedrich, M, Jasinski-Bergner, S, Lazaridou, MF, Subbarayan, K, Massa, C, Tretbar, S, Mueller, A, Handke, D, Biehl, K, Bukur, J, Donia, M, Mandelboim, O & Seliger, B 2019, 'Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy', Cancer Immunology, Immunotherapy, vol. 68, no. 10, pp. 1689-1700. https://doi.org/10.1007/s00262-019-02373-1

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AU - Friedrich, Michael

AU - Jasinski-Bergner, Simon

AU - Lazaridou, Maria Filothei

AU - Subbarayan, Karthikeyan

AU - Massa, Chiara

AU - Tretbar, Sandy

AU - Mueller, Anja

AU - Handke, Diana

AU - Biehl, Katharina

AU - Bukur, Jürgen

AU - Donia, Marco

AU - Mandelboim, Ofer

AU - Seliger, Barbara

N1 - Funding Information: This work was funded by the German Research Foundation (DFG; SE 581/22-1 and RTG, 1591/2-B4), the German Israeli Foundation for Scientific Research and Development (GIF; I-37-414.11-2016), and the Mildred Scheel Foundation. Acknowledgements Publisher Copyright: © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Immunotherapy aims to activate the immune system to fight cancer in a very specific and targeted manner. Despite the success of different immunotherapeutic strategies, in particular antibodies directed against checkpoints as well as adoptive T-cell therapy, the response of patients is limited in different types of cancers. This attributes to escape of the tumor from immune surveillance and development of acquired resistances during therapy. In this review, the different evasion and resistance mechanisms that limit the efficacy of immunotherapies targeting tumor-associated antigens presented by major histocompatibility complex molecules on the surface of the malignant cells are summarized. Overcoming these escape mechanisms is a great challenge, but might lead to a better clinical outcome of patients and is therefore currently a major focus of research.

AB - Immunotherapy aims to activate the immune system to fight cancer in a very specific and targeted manner. Despite the success of different immunotherapeutic strategies, in particular antibodies directed against checkpoints as well as adoptive T-cell therapy, the response of patients is limited in different types of cancers. This attributes to escape of the tumor from immune surveillance and development of acquired resistances during therapy. In this review, the different evasion and resistance mechanisms that limit the efficacy of immunotherapies targeting tumor-associated antigens presented by major histocompatibility complex molecules on the surface of the malignant cells are summarized. Overcoming these escape mechanisms is a great challenge, but might lead to a better clinical outcome of patients and is therefore currently a major focus of research.

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Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy

Abstract

Bibliographical note

Keywords

UN SDGs

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