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@ARTICLE{Wang:288826,
      author       = {Y. Wang and X. Yang and J. Ma and S. Chen and P. Gong and
                      P. Dai$^*$},
      title        = {{T}hyroid dysfunction ({TD}) induced by {PD}-1/{PD}-{L}1
                      inhibitors in advanced lung cancer.},
      journal      = {Heliyon},
      volume       = {10},
      number       = {5},
      issn         = {2405-8440},
      address      = {London [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2024-00491},
      pages        = {e27077},
      year         = {2024},
      note         = {#LA:E055#},
      abstract     = {Thyroid Dysfunction (TD) is a common immune-related adverse
                      events (irAEs) in the treatment of advanced lung cancer with
                      programmed cell death protein 1 (PD-1) and programmed death
                      1 ligand (PD-L1) inhibitors, with incidence accounting for
                      $6-8\%$ of all irAEs. The incidence of TD is receiving
                      increasing attention from clinicians, given its potential
                      impact on clinical efficacy. However, the molecular
                      mechanisms, biomarkers, and clinical impact of TD resulting
                      from PD-1/PD-L1 inhibitor treatment in advanced lung cancer
                      are unclear.To present a comprehensive review of current
                      advancements in research about the molecular mechanisms,
                      influential factors, and clinical manifestations in the
                      treatment of advanced lung cancer with PD-1 and PD-L1
                      inhibitors, as well as the correlation between TD and the
                      efficacy of PD-1 and PD-L1 inhibitors.A systematic search
                      was conducted using PubMed, Web of Science, Cochrane
                      Library, Embase and Google Scholar databases, with the
                      keywords including thyroid dysfunction, efficacy,
                      mechanisms, immune checkpoint inhibitors, PD-1/PD-L1
                      inhibitors, and advanced lung cancer.PD-1/PD-L1 inhibitors
                      can induce T cell-mediated destructive thyroiditis, thyroid
                      autoantibody-mediated autoimmunity, and a decrease in the
                      number of immunosuppressive monocytes (circulating cluster
                      of differentiation (CD)14+ human leukocyte antigen
                      (HLA)-DRlow/negatives monocytes, CD14+ HLA-DR + lo/neg),
                      leading to TD. Several factors, including peripheral blood
                      inflammatory markers, body mass index (BMI), baseline
                      thyroid-stimulating hormone (TSH) level, gender, smoking
                      history, hypertension, and previous opioid use, may also
                      contribute to the development of TD. However, there is
                      currently a lack of reliable predictive biomarkers for TD,
                      although anti-thyroid antibodies, TSH levels, and peripheral
                      blood inflammatory markers are expected to be
                      predictive.Interestingly, some studies suggested a positive
                      correlation between TD and clinical efficacy, i.e., patients
                      experiencing TD showed better outcomes in objective response
                      rate (ORR), disease control rate (DCR), progression-free
                      survival (PFS), and overall survival (OS), compared with
                      those without TD. However, most of these studies were
                      single-center and had small sample sizes, so more
                      multi-center studies are needed to provide further data
                      support.TD resulting from PD-1/PD-L1 inhibitor treatment in
                      advanced lung cancer may be associated with good clinical
                      outcomes. The clarification of the molecular mechanisms
                      underlying TD and the identification of reliable predictive
                      biomarkers will guide clinicians in managing TD in this
                      patient population.},
      subtyp        = {Review Article},
      keywords     = {Advanced lung cancer (Other) / Efficacy (Other) / Immune
                      checkpoint inhibitors (Other) / PD-1/PD-L1 inhibitors
                      (Other) / Thyroid dysfunction (Other)},
      cin          = {E055},
      ddc          = {000},
      cid          = {I:(DE-He78)E055-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38449616},
      pmc          = {pmc:PMC10915392},
      doi          = {10.1016/j.heliyon.2024.e27077},
      url          = {https://inrepo02.dkfz.de/record/288826},
}