2026-09-14T22:39:15Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/277062026-09-12T00:16:48Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Galán, Miguel author Hernández-García, Elena author Munné, Pablo author Redondo-Urzainqui, Ana author Cueto, Francisco J author Sicilia, Jon author Alejano, Sergio Callejas author Rey-Martín, M Ascensión author Dopazo, Ana author Sancho, David author Iborra, Salvador author 2026 Tyrosine kinases and phosphatases regulate protein phosphorylation and maintain cellular homeostasis. The phosphoprotein tyrosine phosphatase SHP-1 (encoded by the gene) has been proposed as an immune checkpoint in CD8 T cells in preclinical models, yet its pharmacological inhibition has shown no efficacy against tumor growth in clinical trials. This suggests that SHP-1 may play opposing roles in different cell types within the tumor microenvironment. Here, we investigated the effect of depleting SHP-1 in CD11c cells on the anti-tumoral response. To dissect the specific role of SHP1 in CD11c antigen-presenting cells, or specifically in conventional type 1 dendritic cells (cDC1s) or macrophages, we subcutaneously inoculated different tumors in , Δ and Δ mice, respectively. Tumor growth and survival were monitored, and immune infiltrates were analyzed using flow cytometry or scRNA-seq. Tumor rejection was impaired when SHP-1 was depleted in CD11c cells, as well as in XCR1 or Lyz2 cells. scRNA-seq analysis revealed that both tumor-associated macrophages and cDC1s exhibited downregulation of interferon response pathways in tumor-bearing mice compared with controls. Reduced MHC-II expression in tumor-associated macrophages was validated by flow cytometry, supporting impaired antigen presentation in these cells, whereas cDC subsets displayed heterogeneous alterations in co-stimulatory marker expression rather than a defect. Consistent with these findings, flow cytometry analysis showed that mice injected with MC38 tumor and treated with anti-PD1 displayed a reduction in CD8 IFN-γ cells in comparison with littermates. These results show that SHP-1 depletion in CD11c cells impairs anti-tumor immunity and suggest that both cDC1s and macrophages contribute to this effect. Front Immunol. 2026 Apr 21:17:1710547. FRONTIERS IN IMMUNOLOGY 42093998 https://hdl.handle.net/20.500.12105/27706 CD8+ T cell response SHP-1 conventional type 1 dendritic cells macrophages tumor rejection Loss of SHP-1 in CD11c cells impairs anti-tumor immunity.