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Inhibition of galectin-3 augments the antitumor efficacy of PD-L1 blockade in non-small-cell lung cancer.
Zhang, Hongxin; Liu, Pengfei; Zhang, Yan; Han, Lujun; Hu, Zhihui; Cai, Ziqi; Cai, Jianhui.
Afiliação
  • Zhang H; Department of Surgery, Hebei Medical University, Shijiazhuang, China.
  • Liu P; Department of Oncology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, China.
  • Zhang Y; Department of Oncology, Shijiazhuang First Hospital, China.
  • Han L; Department of Oncology, Shijiazhuang First Hospital, China.
  • Hu Z; Department of Oncology, Shijiazhuang First Hospital, China.
  • Cai Z; Hebei Engineering Technology Research Center for Cell Therapy, Hebei HOFOY Bio-Tech Co. Ltd, Shijiazhuang, China.
  • Cai J; Department of Surgery, Hebei Medical University, Shijiazhuang, China.
FEBS Open Bio ; 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33455075
ABSTRACT
Multiple clinical trials have shown that monoclonal antibodies (mAbs) against programmed death-ligand 1 (PD-1/PD-L1) can benefit patients with lung cancer by increasing their progression-free survival and overall survival. However, a significant proportion of patients do not respond to anti-PD-1/PD-L1 mAbs. In the present study, we investigated whether galectin (Gal)-3 inhibitors can enhance the antitumor effect of PD-L1 blockade. Using the NSCLC-derived cell line A549, we examined the expression of Gal-3 in lung cancer cells under hypoxic conditions and investigated the regulatory effect of Gal-3 on PD-L1 expression, which is mediated by the STAT3 pathway. We also explored whether Gal-3 inhibition can facilitate the cytotoxic effect of T cells induced by PD-L1 blockade. The effects of combined use of a Gal-3 inhibitor and PD-L1 blockade on tumor growth and T-cell function were also investigated, and we found that hypoxia increased the expression and secretion of Gal-3 by lung cancer cells. Gal-3 increased PD-L1 expression via the upregulation of STAT3 phosphorylation, and administration of a Gal-3 inhibitor enhanced the effect of PD-L1 blockade on the cytotoxic activity of T cells against cancer cells in vitro. In a mouse xenograft model, the combination of a Gal-3 inhibitor and PD-L1 blockade synergistically suppressed tumor growth. Furthermore, the administration of a Gal-3 inhibitor enhanced T-cell infiltration and granzyme B release in tumors. Collectively, our results show that Gal-3 increases PD-L1 expression in lung cancer cells and that the administration of a Gal-3 inhibitor as an adjuvant enhanced the antitumor activity of PD-L1 blockade.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: China

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Artigo País de afiliação: China