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1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol treatment inhibits abnormal tumor growth by regulating neutrophil infiltration in a non-small cell lung carcinoma mouse model.
Kim, Guentae; Kim, Eun Young; Lee, Hyowon; Shin, Su-Hyun; Lee, Se Hee; Sohn, Ki-Young; Kim, Jae Wha; Lee, Jae Sam.
Afiliación
  • Kim G; Enzychem Lifesciences, 14F aT Center 27 Gangnam-daero, Seoul, South Korea; Biotoxtech, 53 Yeongudanji-ro, Ochang-eup, Cheongju-si, South Korea.
  • Kim EY; Enzychem Lifesciences, 14F aT Center 27 Gangnam-daero, Seoul, South Korea.
  • Lee H; Enzychem Lifesciences, 14F aT Center 27 Gangnam-daero, Seoul, South Korea.
  • Shin SH; Enzychem Lifesciences, 14F aT Center 27 Gangnam-daero, Seoul, South Korea.
  • Lee SH; Enzychem Lifesciences, 14F aT Center 27 Gangnam-daero, Seoul, South Korea.
  • Sohn KY; Enzychem Lifesciences, 14F aT Center 27 Gangnam-daero, Seoul, South Korea.
  • Kim JW; Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Kwahak-ro, Daejeon, South Korea.
  • Lee JS; Enzychem Lifesciences, 14F aT Center 27 Gangnam-daero, Seoul, South Korea. Electronic address: jaesam.lee@enzychem.com.
Biomed Pharmacother ; 178: 117269, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39137654
ABSTRACT
Excessive neutrophil infiltration into the tumor microenvironment (TME) is an important factor that contributes to tumor overgrowth and limited immunotherapy efficacy. Neutrophils activate various receptors involved in tumor progression, while suppressing the infiltration and activity of cytotoxic T cells and creating optimal conditions for tumor growth. Therefore, the appropriate control of neutrophil infiltration is an effective strategy for tumor treatment. In the present study, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) inhibited tumor overgrowth by suppressing excessive neutrophil infiltration, resulting in >74.97 % reduction in tumor size in a Lewis lung carcinoma (LLC-1) mouse model. All subjects in the positive control group died during the 90-day survival period, whereas only four subjects in the PLAG treatment group survived. PLAG had a significantly higher tumor growth inhibitory effect and survival rate than other neutrophil infiltration-targeting inhibitors (e.g., Navarixin, lymphocyte antigen 6 complex locus G6D antibody [aLy6G]). The ability of PLAG to regulate neutrophil infiltration and inhibit tumor growth depends on thioredoxin-interacting protein (TXNIP). In tumors lacking TXNIP expression, PLAG failed to control neutrophil infiltration and infiltration-related factor release, and the inhibitory effect of PLAG on tumor growth was reduced. PLAG-mediated inhibition of neutrophil infiltration enhances the efficacy of immune checkpoint inhibitors (ICIs), increasing the antitumor efficacy and survival rate by 30 %. In conclusion, PLAG could be a novel alternative to anti-tumor drugs that effectively targets excessive neutrophil infiltration into cancer tissues.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Carcinoma Pulmonar de Lewis / Infiltración Neutrófila / Microambiente Tumoral / Neoplasias Pulmonares / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Carcinoma Pulmonar de Lewis / Infiltración Neutrófila / Microambiente Tumoral / Neoplasias Pulmonares / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article Pais de publicación: Francia