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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 Vandsemb  3 , Roy S Herbst  2 , Lieping Chen  4   5
Affiliations
Review

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

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

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

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