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Activation of NOD1 on tumor-associated macrophages augments CD8+ T cell-mediated antitumor immunity in hepatocellular carcinoma.
Zhang, Feng; Jiang, Qiuyu; Cai, Jialiang; Meng, Fansheng; Tang, Wenqing; Liu, Zhiyong; Lin, Xiahui; Liu, Wenfeng; Zhou, Yi; Shen, Xizhong; Xue, Ruyi; Dong, Ling; Zhang, Si.
Afiliação
  • Zhang F; Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Jiang Q; Shanghai Institute of Liver Disease, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Cai J; Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Meng F; Shanghai Institute of Liver Disease, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Tang W; Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Liu Z; Shanghai Institute of Liver Disease, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Lin X; Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Liu W; Shanghai Institute of Liver Disease, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Zhou Y; Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Shen X; Shanghai Institute of Liver Disease, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Xue R; Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Dong L; Shanghai Institute of Liver Disease, 180 Fenglin Road, Shanghai, 200032, P.R. China.
  • Zhang S; Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Sci Adv ; 10(40): eadp8266, 2024 Oct 04.
Article em En | MEDLINE | ID: mdl-39356756
ABSTRACT
The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway in hepatocellular carcinoma (HCC) is limited. NOD-like receptors (NLRs) comprise a highly evolutionarily conserved family of cytosolic bacterial sensors, yet their impact on antitumor immunity against HCC remains unclear. In this study, we uncovered that NOD1, a well-studied member of NLR family, exhibits predominant expression in tumor-associated macrophages (TAMs) and correlates positively with improved prognosis and responses to anti-PD-1 treatments in patients with HCC. Activation of NOD1 in vivo augments antitumor immunity and enhances the effectiveness of anti-PD-1 therapy. Mechanistically, NOD1 activation resulted in diminished expression of perilipin 5, thereby hindering fatty acid oxidation and inducing free fatty acid accumulation in TAMs. This metabolic alteration promoted membrane localization of the costimulatory molecule OX40L in a lipid modification-dependent manner, thereby activating CD8+ T cells. These findings unveil a previously unrecognized role for NOD1 in fortifying antitumor T cell immunity in HCC, potentially advancing cancer immunotherapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Linfócitos T CD8-Positivos / Proteína Adaptadora de Sinalização NOD1 / Macrófagos Associados a Tumor / Neoplasias Hepáticas Limite: Animals / Humans / Male Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Linfócitos T CD8-Positivos / Proteína Adaptadora de Sinalização NOD1 / Macrófagos Associados a Tumor / Neoplasias Hepáticas Limite: Animals / Humans / Male Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos