Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities

doi:10.1038/s41573-022-00493-5

Review

. 2022 Jul;21(7):529-540.

doi: 10.1038/s41573-022-00493-5. Epub 2022 Jun 14.

Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities

Tae Kon Kim^{1

2}, Esten N Vandsemb³, Roy S Herbst², Lieping Chen^{4

5}

Affiliations

¹ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
² Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA.
³ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA. lieping.chen@yale.edu.
⁵ Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. lieping.chen@yale.edu.

PMID: 35701637
DOI: 10.1038/s41573-022-00493-5

Review

Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities

Tae Kon Kim et al. Nat Rev Drug Discov. 2022 Jul.

. 2022 Jul;21(7):529-540.

doi: 10.1038/s41573-022-00493-5. Epub 2022 Jun 14.

Authors

Tae Kon Kim^{1

2}, Esten N Vandsemb³, Roy S Herbst², Lieping Chen^{4

5}

Affiliations

¹ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
² Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA.
³ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA. lieping.chen@yale.edu.
⁵ Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. lieping.chen@yale.edu.

PMID: 35701637
DOI: 10.1038/s41573-022-00493-5

Abstract

Tumours employ various tactics to adapt and eventually resist immune attack. These mechanisms are collectively called adaptive immune resistance (AIR). The first defined and therapeutically validated AIR mechanism is the selective induction of programmed cell death 1 ligand 1 (PDL1) by interferon-γ in the tumour. Blockade of PDL1 binding to its receptor PD1 by antibodies (anti-PD therapy) has resulted in remission of a fraction of patients with advanced-stage cancer, especially in solid tumours. However, many clinical trials combining anti-PD therapy with other antitumour drugs conducted without a strong mechanistic rationale have failed to identify a synergistic or additive effect. In this Perspective article, we discuss why defining AIR mechanisms at the tumour site should be a key focus to direct future drug development as well as practical approaches to improve current cancer therapy.

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References

1. Dong, H., Zhu, G., Tamada, K. & Chen, L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365–1369 (1999). This article is the first to report the molecular cloning of B7-H1 (also called PDL1) and demonstration of its immunosuppressive function. - PubMed - DOI
1. Freeman, G. J. et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 192, 1027–1034 (2000). This article reports that PDL1 could interact with PD1 to inhibit T cell activity. - PubMed - PMC - DOI
1. Dong, H. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793–800 (2002). This is the first paper to demonstrate that PDL1 expressed on tumour cells induces immune evasion by suppressing T cells, that PDL1 can be upregulated by IFNγ, and finally, it also shows the therapeutic effect of an antibody that blocks the PD1–PDL1 interaction. - PubMed - DOI
1. Dong, H. et al. B7-H1 determines accumulation and deletion of intrahepatic CD8⁺ T lymphocytes. Immunity 20, 327–336 (2004). - PubMed - DOI
1. Parish, C. R. Cancer immunotherapy: the past, the present and the future. Immunol. Cell Biol. 81, 106–113 (2003). - PubMed - DOI

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[1] Dong, H., Zhu, G., Tamada, K. & Chen, L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365–1369 (1999). This article is the first to report the molecular cloning of B7-H1 (also called PDL1) and demonstration of its immunosuppressive function. - PubMed - DOI

[2] Dong, H., Zhu, G., Tamada, K. & Chen, L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365–1369 (1999). This article is the first to report the molecular cloning of B7-H1 (also called PDL1) and demonstration of its immunosuppressive function. - PubMed - DOI

[3] Freeman, G. J. et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 192, 1027–1034 (2000). This article reports that PDL1 could interact with PD1 to inhibit T cell activity. - PubMed - PMC - DOI

[4] Freeman, G. J. et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 192, 1027–1034 (2000). This article reports that PDL1 could interact with PD1 to inhibit T cell activity. - PubMed - PMC - DOI

[5] Dong, H. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793–800 (2002). This is the first paper to demonstrate that PDL1 expressed on tumour cells induces immune evasion by suppressing T cells, that PDL1 can be upregulated by IFNγ, and finally, it also shows the therapeutic effect of an antibody that blocks the PD1–PDL1 interaction. - PubMed - DOI

[6] Dong, H. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793–800 (2002). This is the first paper to demonstrate that PDL1 expressed on tumour cells induces immune evasion by suppressing T cells, that PDL1 can be upregulated by IFNγ, and finally, it also shows the therapeutic effect of an antibody that blocks the PD1–PDL1 interaction. - PubMed - DOI

[7] Dong, H. et al. B7-H1 determines accumulation and deletion of intrahepatic CD8⁺ T lymphocytes. Immunity 20, 327–336 (2004). - PubMed - DOI

[8] Dong, H. et al. B7-H1 determines accumulation and deletion of intrahepatic CD8⁺ T lymphocytes. Immunity 20, 327–336 (2004). - PubMed - DOI

[9] Parish, C. R. Cancer immunotherapy: the past, the present and the future. Immunol. Cell Biol. 81, 106–113 (2003). - PubMed - DOI

[10] Parish, C. R. Cancer immunotherapy: the past, the present and the future. Immunol. Cell Biol. 81, 106–113 (2003). - PubMed - DOI

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Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities

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Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities

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