Details

Autor(en) / Beteiligte

• dos Santos, Jéssica Cristina
• Moreno, María
• Teufel, Lisa U.
• Chilibroste, Sofía
• Keating, Samuel T.
• Groh, Laszlo
• Domínguez-Andrés, Jorge
• Williams, David L.
• Ma, Zuchao
• Lowman, Douglas W.
• Ensley, Harry E.
• Novakovic, Boris
• Ribeiro-Dias, Fátima
• Netea, Mihai G.
• Chabalgoity, José A.
• Joosten, Leo A.B.

Titel

Leishmania braziliensis enhances monocyte responses to promote anti-tumor activity

Ist Teil von

• Cell reports (Cambridge), 2024-03, Vol.43 (3), p.113932-113932, Article 113932

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Innate immune cells can undergo long-term functional reprogramming after certain infections, a process called trained immunity (TI). Here, we focus on antigens of Leishmania braziliensis, which induced anti-tumor effects via trained immunity in human monocytes. We reveal that monocytes exposed to promastigote antigens of L. braziliensis develop an enhanced response to subsequent exposure to Toll-like receptor (TLR)2 or TLR4 ligands. Mechanistically, the induction of TI in monocytes by L. braziliensis is mediated by multiple pattern recognition receptors, changes in metabolism, and increased deposition of H3K4me3 at the promoter regions of immune genes. The administration of L. braziliensis exerts potent anti-tumor capabilities by delaying tumor growth and prolonging survival of mice with non-Hodgkin lymphoma. Our work reveals mechanisms of TI induced by L. braziliensis in vitro and identifies its potential for cancer immunotherapy. [Display omitted] •Leishmania braziliensis induces trained immunity (TI) in human monocytes•The secondary stimulus dictates the effector responses produced by trained monocytes•L. braziliensis reduces tumor growth and improves survival in solid tumor models•L. braziliensis impacts the myeloid and T cell accumulation in the tumor environment dos Santos et al. report the ability of Leishmania parasites to improve the responses of monocytes through trained immunity. Trained macrophages impact tumor growth and survival of mice bearing lymphoma and melanoma, offering opportunities for the use of trained immunity in cancer therapy.