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Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook

Authors
  • Horvath, Lena1
  • Thienpont, Bernard2
  • Zhao, Liyun2
  • Wolf, Dominik1, 3
  • Pircher, Andreas1
  • 1 Medical University Innsbruck, Anichstraße 35, Innsbruck, 6020, Austria , Innsbruck (Austria)
  • 2 KU Leuven, Herestraat 49, Leuven, 3000, Belgium , Leuven (Belgium)
  • 3 University Hospital Bonn (UKB), Sigmund-Freud-Street 25, Bonn, 53127, Germany , Bonn (Germany)
Type
Published Article
Journal
Molecular Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Sep 11, 2020
Volume
19
Issue
1
Identifiers
DOI: 10.1186/s12943-020-01260-z
Source
Springer Nature
Keywords
License
Green

Abstract

Immunotherapy (IO) has revolutionized the therapy landscape of non-small cell lung cancer (NSCLC), significantly prolonging the overall survival (OS) of advanced stage patients. Over the recent years IO therapy has been broadly integrated into the first-line setting of non-oncogene driven NSCLC, either in combination with chemotherapy, or in selected patients with PD-L1high expression as monotherapy. Still, a significant proportion of patients suffer from disease progression. A better understanding of resistance mechanisms depicts a central goal to avoid or overcome IO resistance and to improve patient outcome. We here review major cellular and molecular pathways within the tumor microenvironment (TME) that may impact the evolution of IO resistance. We summarize upcoming treatment options after IO resistance including novel IO targets (e.g. RIG-I, STING) as well as interesting combinational approaches such as IO combined with anti-angiogenic agents or metabolic targets (e.g. IDO-1, adenosine signaling, arginase). By discussing the fundamental mode of action of IO within the TME, we aim to understand and manage IO resistance and to seed new ideas for effective therapeutic IO concepts.

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